Multiple Organ Dysfunction Syndrome Model Research Articles

Practical Effect of Cervical Softening Decoction Combined with Delivery Ball Approach in Promoting Vaginal Delivery in Primiparous Women

In Traditional Chinese Medicine, Cervical Softening Decoction is derived from a modified “Wan Bing Hui Chun” formulation and consists of natural herbal ingredients such as Angelica sinensis, Ligusticum chuanxiong, Leonurus heterophyllus, and Cortex Daphnes. The decoction regulates Qi, promotes blood circulation, and facilitates fetus descent. Genkwanin is an active compound in L. heterophyllus and previous studies identified this compound in ethanolic extracts from rat uterine smooth muscle cell membrane fractions. To further understand the pharmacological activities of Cervical Softening Decoction, we examined genkwanin effects on isolated rat uterine contractions and protein expression in rat tissue with postpartum hemorrhage complicated by multiple organ dysfunction syndrome (MODS). We also explored the practical effects of Cervical Softening Decoction combined with a birthing ball approach on promoting natural delivery in primiparous women. First, an isolated rat uterine smooth muscle contraction model was generated and three groups established: oxytocin group (0.002 U/mL), conventional genkwanin dose group (3 μg/mL), and high genkwanin dose group (6.0 μg/mL). Changes in uterine smooth muscle contraction and relaxation amplitudes were recorded before and after administration. Second, 50 rats were used to establish the following groups: (1) control group, (2) postpartum hemorrhage with MODS model group (MODS group), and (3) a postpartum hemorrhage with MODS treated with genkwanin group (genkwanin group). Western blotting was used to detect and compare tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 protein expression levels in lung tissue from groups. Finally, 84 primiparous women admitted to our hospital between January 2020 and December 2021 were selected and divided into two groups based on their obstetric interventions. The control group (n = 42) received routine obstetric intervention, while the observation group (n = 42) received Cervical Softening Decoction and delivery ball interventions. Delivery conditions were compared across groups. In basic studies, genkwanin doses significantly increased contraction and relaxation values in isolated rat uterine smooth muscle (P <0.05). Moreover, the genkwanin contractile effects at conventional and high doses were comparable with oxytocin. TNF-α and IL-6 protein expression in MODS group lung tissue was significantly higher when compared with the control group, while expression in the genkwanin group was significantly reduced when compared with the MODS group (P <0.05). In clinical studies, the observation group showed significantly higher natural delivery rates and Labor Agentry Scale (LAS) scores when compared with the control group. In contrast, cesarean section rates, first and second stage labor duration, total labor duration, and Facial Pain Scale (FPS) scores were significantly lower in the observation group when compared with the control group (P <0.05). In basic studies, genkwanin elicited significant contraction effects on isolated rat uterine smooth muscle and effectively inhibited inflammatory responses in rats with postpartum hemorrhage complicated by MODS. In clinical studies, combined Cervical Softening Decoction and delivery ball generated promising practical effects in promoting vaginal delivery in primiparous women. The intervention significantly increased the probability of a natural delivery, shortened labor duration, relieved maternal pain, and enhanced maternal control during delivery.

Modeling Organ Failure Under Hypoxic Stress

Multiple organ dysfunction syndrome (MODS) is one of the leading causes of death in the intensive care unit. Due to the variety of pathophysiological mechanisms that can initiate organ failure, clinicians are challenged in selecting treatments and the literature for modeling the pathogenesis and recovery from MODS is sparse. The present work develops a model of MODS by coupling a game theoretic approach for quantifying organ function with a dynamic model of physiological processes that impact organ health. Organ and system response to high-altitude pulmonary edema are used as a quantitative test case of the model's ability to capture the development of and recovery from organ dysfunction.

Characterization and Hepatoprotections of Ganoderma lucidum Polysaccharides against Multiple Organ Dysfunction Syndrome in Mice.

Background The liver is one of the most commonly affected organs in multiple organ dysfunction syndrome (MODS). In recent years, there have been many studies on Ganoderma lucidum polysaccharides (GLP), but the role of GLP in MODS is still unclear. The purpose of this work was to explore the antioxidant, anti-inflammatory, and protective effects of GLP on the liver in MODS model mice. Methods The characteristic properties of GLP were processed by physicochemical analysis. The MODS models were successfully established with intraperitoneal injection of zymosan in Kunming strain mice. The antioxidant, anti-inflammatory, and hepatoprotective effects of GLP were processed both in vitro and in vivo by evaluating the oxidative parameters, inflammatory factors, and liver pathological observations. Results The characterization analysis revealed that GLP was a pyranose mainly composed of glucose with the molecular weights (Mw) of 8309 Da. The experimental results proved that GLP had potential hepatoprotection possibly by improving the antioxidant status (scavenging excessive oxygen radicals, increasing the antioxidant enzyme activities, and reducing the lipid peroxide), alleviating the inflammatory response (reducing the inflammatory factor levels), and guaranteeing the liver functions. Conclusions This research suggested that GLP had the potential to be developed as a natural medicine for the treatment of multiple organ failure.

Potential Role of Caveolin-1 in Regulating the Function of Endothelial Progenitor Cells from Experimental MODS Model.

Multiple organ dysfunction syndrome (MODS) remains a great challenge in critical care because of its common occurrence, high cost of care, and high mortality. Vascular endothelial injury is the initiation step in the development of MODS, and EPCs are essential for the process of organ repair. It is unclear whether and how caveolin-1 (Cav-1) in EPCs contributes to the pathogenesis of MODS. The present study is aimed at investigating the potential role of Cav-1 in EPCs during MODS. We established a MODS model in pigs, isolated and characterized EPCs from the MODS model, and tracked Cav-1 expression and various in vitro behaviors of EPCs from the MODS model. Then, we knockdown Cav-1 expression with siRNA or induce Cav-1 expression with proinflammatory factors to evaluate potential effects on EPCs. Our results suggest that Cav-1 expression correlated with EPC functions during MODS and Cav-1 regulates the function of endothelial progenitor cells via PI3K/Akt/eNOS signaling during MODS. Thus, Cav-1 in EPCs could be an attractive target for the treatment of MODS.

RNA inhibitors of nuclear proteins responsible for multiple organ dysfunction syndrome

The development of multiple organ dysfunction syndrome (MODS) following infection or tissue injury is associated with increased patient morbidity and mortality. Extensive cellular injury results in the release of nuclear proteins, of which histones are the most abundant, into the circulation. Circulating histones are implicated as essential mediators of MODS. Available anti-histone therapies have failed in clinical trials due to off-target effects such as bleeding and toxicity. Here, we describe a therapeutic strategy for MODS based on the neutralization of histones by chemically stabilized nucleic acid bio-drugs (aptamers). Systematic evolution of ligands by exponential enrichment technology identified aptamers that selectively bind those histones responsible for MODS and do not bind to serum proteins. We demonstrate the efficacy of histone-specific aptamers in human cells and in a murine model of MODS. These aptamers could have a significant therapeutic benefit in the treatment of multiple diverse clinical conditions associated with MODS.

Identification of genes and pathways associated with multiple organ dysfunction syndrome by microarray analysis.

Multiple organ dysfunction syndrome (MODS) is characterized by the development of progressive physiological dysfunction of ≥2 organs or organ systems and is responsible for the majority of the morbidity and mortality among patients in intensive care units. The aim of the present study was to investigate the potential genes and pathways associated with MODS. The microarray dataset GSE60088 was downloaded from the Gene Expression Omnibus and used to identify differentially expressed genes (DEGs) between organ tissues (lung, liver and kidney) obtained from a murine model of MODS and healthy controls. The interactions between DEGs in lungs, liver and kidneys were revealed by Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Furthermore, protein-protein interaction (PPI) data for DEGs were obtained from the Search Tool for the Retrieval of Interacting Genes and a PPI network was constructed. Additionally, DEGs that were common among the three organs were screened and transcription factors that regulated them were predicted using the iRegulon plugin. A total of 943, 267 and 227 DEGs were identified in lung, liver and kidney samples, respectively, between mice with MODS and healthy controls. In lung and liver samples, two pathways that were enriched with DEGs were identified and were common between lung and liver samples, including ‘cytokine-cytokine receptor interaction’ and ‘Jnk-STAT signaling pathway’, and examples of DEGs associated with these pathways include C-X-C motif chemokine ligand (Cxcl)1 and Cxcl10, and signal transducer and activator of transcription (Stat)1, respectively. Furthermore, two common pathways were identified in liver and kidney samples, which included ‘MAPK signaling pathway’ and ‘p53 signaling pathway’, and DEGs associated with these pathways included growth arrest and DNA damage-inducible α. A total of 18 DEGs were common among lung, liver and kidney tissues, including CCAAT/enhancer binding protein β (Cebpb) and olfactomedin-like 1 (Olfml1). Cebpb modulated various other DEGs, such as Cxcl1, and Olfml1 was regulated by Stat5A. These genes and pathways may serve roles in the progression of MODS and may be considered to be potential therapy targets for MODS.

The role of HMGB1 in BMSC transplantation for treating MODS in rats.

The effect of bone marrow mesenchymal stem cells (BMSCs) in treatment for multiple organ dysfunction syndrome (MODS) remains unknown and the mechanism is still unclear. Therefore, the goal of this study is to investigate the effects of intracellular high mobility group box 1 protein (HMGB1) on BMSCs treating for MODS. The rats were given 15% blood loss plus 1mg/kg lipopolysaccharide (LPS) via lower extremity superficial venous, then randomly allocated into four groups: sham group, MODS group, MODS plus BMSC group, MODS plus ethyl pyruvate (EP) group, MODS plus BMSCs plus EP group. Twenty-four hours later, rats in groups were sacrificed and then the blood and tissues were collected to evaluate the changes of tissue histopathology, cell apoptosis, inflammation level and organ function. The HGMB1 expression was monitored by RT-qPCR and Western blot. The expression of RAGE/TLR2/TLR4 and NF-κB at the protein levels was also assessed. BMSCs and/or EP exhibits an outstanding protective effect against LPS-induced histopathological injury by improving cell apoptosis, inflammatory response and the organ dysfunction but no effect on BMSC homing to the injury site. Moreover, BMSCs and/or EP inhibited LPS-induced upregulation of HMGB1, RAGE, TLR2 and TLR4 expression at protein levels and compromised p65 phosphorylation in the rat model of MODS. These findings suggest that HMGB1 is involved in BMSC treatment for MODS, through regulation of the TLR2, TLR4-mediated NF-κB signal pathway. It suggests that HMGB1 is an attractive potential target for the development of new therapeutic strategies for MODS.

Bone marrow mesenchymal stem cells modulated the inflammatory response by regulating the expression of IL-4 and RAGE products in the rats with MODS

To investigate the underlying mechanism of bone marrow mesenchymal stem cells (BMSC) modulating the inflammatory response during the multiple organ dysfunction syndrome (MODS), especially the expression of inflammatory cytokines, which will provide new theoretical and experimental basis of MODS in clinic. BMSC of Sprague-Dawley (SD) rat (female, 4 weeks) was extracted and cultivated, and the 4th passage were used in experimental study. According to the random number table, 60 female SD rats were divided into three groups (n = 20 per group): sham group, MODS group, BMSC group. MODS model in rats was induced by lipopolysaccaride (LPS, 1 mg/kg) via femoral vein injection. Sham group was injected with the sterile phosphate buffer saline (PBS) in the same volume. BMSC group, in which BMSC infusion was started at 2 hours after 0.5 mL LPS stimulation (1×106/cells) through the tail vein. The survival rate was observed after 72 hours in each group. Abdominal aortic blood was collected for routine blood and biochemical examination at 72 hours after operation. Protein microarray was used to detect the related 34 inflammatory cytokines. Signal ratio was defined as the differentially expressed factors when it was more than 2.0 or less than 0.5. And enzyme linked immunosorbent assay (ELISA) was be applied to validate the significant inflammation factor. Meanwhile, the heart, kidney, intestine tissue was harvested, then their pathological changes were observed by hematoxylin eosin (HE) staining. 20, 12, 16 rats lived in sham group, MODS group and BMSC group respectively at 72 hours after operation. Compared with the sham group, the indicators (routine blood, liver and kidney function, myocardial enzyme) were apparently unusual, and the heart, kidney, intestine tissue were injured obviously in the MODS group. After BMSC administration, the organ function was improved and tissue damaged was alleviated significantly. Protein microarray showed that interleukin-4 (IL-4) and receptor for advanced glycation end products (RAGE) were significantly different in 34 goal cytokines. The signal ratio change of IL-4 was 0.397, 1.124, 2.826 respectively, and the signal ratio of RAGE was 6.197, 1.552, 0.250, respectively in MODS/sham group, BMSC/sham group, BMSC/MODS group. ELISA validated the result that the expression level of IL-4 decreased significantly (ng/L: 3.59±1.21 vs. 29.10±5.78) and the expression level of RAGE increased significantly (ng/L: 1.09±0.04 vs. 0.11±0.03) in MODS group as compared with sham group (both P < 0.05). Compared with the MODS group, the level of IL-4 was obviously higher than that in BMSC group (ng/L: 9.59±2.21 vs. 3.59±1.21, P < 0.01), and RAGE decreased significantly (ng/L: 0.29±0.07 vs. 1.09±0.04, P < 0.05). BMSC administration can regulate the expression of IL-4 and RAGE in the rats subjected to MODS. Moreover, BMSC can promote the restoration of tissue and organ function, thus improve the survival rate. BMSC may be the target in cell therapy for the inflammatory disease.

Role of dexmedetomidine in IL-4 and IFN-γ expression in rats with multiple organ dysfunction syndrome induced by postpartum bleeding

Bleeding-induced multiple organ dysfunction syndrome (MODS) is one of the major causes of death in pregnant women. MODS is thought to result from an inappropriate generalized host inflammatory response to a variety of acute insults. In this study we established a MODS model in postpartum rats, in which MODS was induced by the combination of induced hypotension for 60 min and clamping of the superior mesenteric artery for a period of 40 min. We sacrificed all the rats 24 h after dexmedetomidine (DEX) treatment. Thymus, spleen, and mesenteric lymph node tissue were collected to detect interferon-γ (IFN-γ) and interleukin-4 (IL-4) protein expression; lung and intestine tissue were collected to measure IFN-γ and IL-4 gene expression. In the present study, IFN-γ and IL-4 mRNA were increased in the lungs and intestines of the MODS rats. DEX administration decreased IFN-γ and IL-4 mRNA expression. IFN-γ and IL-4 expression for the thymus, spleen, and mesenteric lymph nodes were higher in the MODS postpartum rats relative to control rats, and these expression levels decreased upon DEX administration, But there were no significant differences between DEX doses. In conclusion DEX administration appeared to reduce IFN-γ and IL-4 protein expression in thymus, spleen, and mesenteric lymph node tissue and reduce IFN-γ and IL-4 gene expression in the lungs and intestines in the MODS postpartum rats but was not dose-dependent.

Apoptosis of interstitial cells of Cajal in deep muscular layer of small intestine in rats with multiple organ dysfunction syndrome

To observe the apoptosis of interstitial cells of Cajal in deep muscular layer (ICC-DMP) of small intestine in rats with multiple organ dysfunction syndrome (MODS) as a result of bacterial peritonitis, and the expression of c-kit (an ICC phenotype marker) and Bax/Bcl-2, in order to investigate the mechanism of gastrointestinal motility dysfunction in MODS. According to the random number table, 40 Wistar rats were randomly divided into two groups: control group (n=20) and MODS group (n=20). The MODS model in rats was reproduced by intraperitoneal injection of 8×10(8) cfu/mL Escherichia coli suspension 1 mL, and the control group was given the same amount of normal saline. After 24 hours, the upper small intestine was harvested for examination. Ultrastructure of ICC-DMP was observed using electron microscope. The network structure of ICC-DMP and the expression of c-kit and Bax/Bcl-2 were observed and determined with immunofluorescence and laser scanning confocal microscope. Macroscopic observation revealed that the gastrointestinal motility of rats was normal in the control group. Compared with the control group, gastro intestine was significantly expanded with parulytic ileus in MODS group. It was shown by transmission electron microscopy that intermediate filament structure of ICC-DMP was clear without swelling of mitochondria; chromatin distributed uniformly with small amounts of heterochromatin aggregated in perinuclear. Compared with the control group, intermediate filament structure of ICC-DMP was fuzzy, and mitochondria were swollen obviously in MODS group; chromatin was assembled in nucleus centre. It was shown by laser scanning confocal microscope that the network structure of ICC-DMP was clear, the expression of c-kit and Bcl-2 was strongly and overlapping; the expression of Bax was weak and scatter distributed. Compared with control group, ICC-DMP quantity in MODS group was significantly reduced (cells/HP: 15.80±2.30 vs. 25.70±3.97, t=6.819, P=0.000 ), and ICC network was incomplete. The expression of c-kit and Bcl-2 was significantly decreased as compared with control group [ c-kit (fluorescence intensity): 129.56±36.90 vs. 307.23±40.07, t=10.314, P=0.000; Bcl-2 (fluorescence intensity): 103.23±25.19 vs. 378.92±43.79, t=17.259, P=0.000], whereas, the expression of Bax was significantly increased (fluorescence intensity: 270.94±36.98 vs. 92.57±20.92, t=-13.277, P=0.000 ). The mechanism of gastrointestinal motility dysfunction in MODS maybe closely related to ultrastructural damage of ICC-DMP, changes of c-kit phenotypic and activation of mitochondrial apoptosis pathway.

Modulation of endothelial progenitor cells by tumor necrosis factor-α in multiple organ dysfunction syndrome in swine

To study the modulation in number and function of endothelial progenitor cell (EPC) in multiple organ dysfunction syndrome (MODS) after trauma in swine, and to investigate its pathogenesis. Forty pigs were divided into sham group and MODS group (each, n=20). The model of MODS of "two-hit" injury, namely hemorrhagic shock and endotoxemia, was reproduced. The peripheral blood was collected before hemorrhage (T1) and endotoxin injection (T2), and 1 hour (T3), 24 hours (T4), 48 hours (T5) after endotoxin injection. Phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK ) in mononuclear cell was determined by Western Blot, the content of tumor necrosis factor-α (TNF-α) was determined with enzyme linked immunosorbent assay (ELISA), and the number of EPC was determined with flow cytometry. Model of MODS was successfully reproduced in 17 pigs. In model group, the expression of p-p38MAPK (A value) peaked at T3 (4.83±0.52), and gradually declined at T4 and T5 (4.36±0.43, 1.93±0.33), and the expression of p-p38MAPK at T3-T5 was significantly higher than that at T1 (1.00±0.22, all P<0.01). The plasma concentration of TNF-α (ng/L) at T3 in MODS group was obviously elevated compared with that of sham group (532.43±52.17 vs. 129.03±20.45, t=31.163, P<0.001), and it peaked at T3, it then gradually lowered, and it was significantly higher at T4 and T5 than that in sham group (T4: 398.93±35.75 vs. 131.12±29.53, t=26.562, P<0.001; T5: 287.48±27.26 vs. 126.44±26.96, t=17.861, P<0.001). The number of EPC (×10(7)/L) was apparently increased in MODS group at T3 compared with sham group (4.832±0.624 vs. 3.545±0.363, t=9.542, P<0.001), and it peaked at T3, then gradually decreased, and the number of EPC at T4 and T5 was significantly lower than that in sham group (T4: 2.628±0.627 vs. 3.442±0.325, t=5.043, P<0.001; T5: 2.203±0.711 vs. 3.471±0.323, t=2.972, P<0.001). Phosphorylation of p38MAPK could increase the plasma concentration of TNF-αand decrease the quantity of EPC in MODS,which may be one of the mechanisms of MODS.

Effects of Dachengqi Decoction () on morphological changes in enteric nerve system of rats with multiple organ dysfunction syndrome.

To observe the morphological changes in enteric nerve system (ENS) of rats with multiple organ dysfunction syndrome (MODS) treated by Dachengqi Decoction (, DCQD). Fifty Wistar rats were randomly assigned to the control group, MODS model group and DCQD treated group. The rats in MODS model group and DCQD treated group were injected Escherichia coli (E. coli) suspension into abdominal cavity under sterile condition. The DCQD treated group was gavaged with DCQD 2 days before the E. coli suspension was injected. Twenty-four hours after injection, the proximal segment of intestine was resected and studied by immunohistofluorescence using vesicular acetylcholine transporter, vasoactive intestinal polypeptide (VIP), substance P (SP) and neuronal nitric oxide synthase (nNOS) antibodies. The whole-mount preparations were observed by laser scanning confocal microscope to detect the changes of quantity and fluorescence integral optical density (IOD) value of intestine enteric nerves. Compared with the control group, the quantity and IOD value of acetylcholine (ACh), VIP, SP and nitric oxide (NO) nerves of intestine in the MODS group were significantly decreased (P<0.01), and the network of enteric nerves was remarkably disrupted. Compared with the MODS group, the quantity and fluorescence IOD value of ACh, VIP, SP and NO nerves in the DCQD group were significantly increased (P<0.01), and the network of enteric nerves was remarkably recovered. DCQD can protect and repair damage in the network of ACh, SP, NO and VIP nerves in rats with MODS, which may be one of mechanisms involved in promoting gastrointestinal motility by DCQD.

Mitigation of the damage of intestinal smooth muscle of rats with multiple organ dysfunction syndrome by Dachengqi decoction through mitochondrial pathway

To discuss the mechanism of promotion of gastrointestinal motility during multiple organ dysfunction syndrome (MODS) by Dachengqi decoction, by examining the expression of Bcl-2, Bax of mitochondrial pathway, and nuclear factor-ΚB (NF-ΚB) in smooth muscle of the small intestinal in rats. According to the random number table, 100 healthy adult Wistar rats were divided into three groups: control group with 20 rats, model group with 40 rats, and Dachengqi decoction group with 40 rats. Rat model of MODS was reproduced by bacterial peritonitis induced by an injection of 1 mL Escherichia coli suspension (8×10(8) cfu/mL) into peritoneal cavity. The rats in control group were given 1 mL normal saline intraperitoneally. The rats in Dachengqi decoction group were given 10 mL/kg Dachengqi decoction by gavage, twice a day, before inoculation of the bacterial suspension. Twenty-four hours after modelling, rats in all groups were sacrificed by cervical vertebra luxation, and the upper small intestine was harvested to detect the protein expressions of Bcl-2, Bax, and NF-ΚB in smooth muscle tissue using immunohistochemical staining. In the control group, a large amount of Bcl-2 protein was expressed and it was distributed uniformly in small intestinal smooth muscle. On the other hand, a small amount of Bax and NF-ΚB protein was expressed, and they were also distributed uniformly. Compared with the control group, Bcl-2 protein was distributed only sparsely, and it was scattered in intestinal smooth muscle in blocks in the model group. The expression of Bcl-2 protein was obviously down-regulated [integral optical density (A) value: 7 115.3±1 797.2 vs. 22 085.5±4 892.2, P < 0.05], and this phenomenon was more prominent in circular muscle layer. Bax and NF-ΚB were densely distributed, and their expressions were upgraded obviously [Bax (A value): 33 802.6±5 778.0 vs. 7 984.4±1 804.5, NF-ΚB (A value): 2 465.9±664.8 vs. 1 572.6±256.0, both P < 0.05]. This phenomenon was more outstanding in circular muscle layer. Compared with that of the model group, the expression of Bcl-2 protein was stronger obviously in intestinal smooth muscle in Dachengqi decoction group (A value: 12 458.6±2 491.1 vs. 7 115.3±1 797.2, P < 0.05). The expressions of Bax and NF-ΚB were down-regulated obviously [Bax (A value): 12 529.2±2 018.5 vs. 33 802.6±5 778.0, NF-ΚB (A value): 1 843.1±373.6 vs. 2 465.9±664.8, both P < 0.05], and the change was more obvious in circular muscle layer. Dachengqi decoction may promote recovery of gastrointestinal motility through an increase of Bcl-2 expression in nuclear membrane, thus preventing translocation of Bax to mitochondrion, thereby reduces mitochondrial damage in MODS.

Protein expression levels in the medullary visceral zone of rats with subarachnoid hemorrhage.

We investigated protein expression in the medullary visceral zone (MVZ) of rats with multiple-organ dysfunction syndrome (MODS) caused by subarachnoid hemorrhage (SAH) to discuss the possible regulatory mechanism of the MVZ in the course of SAH-induced MODS. A SAH-induced MODS model was established in rats by injecting arterial blood into the Willis' circle. Protein expression in the MVZ was analyzed by immunohistochemistry assay. Protein expression in the MVZ peaked 24-36 h after SAH, and was significantly higher than in the control and sham operation groups. Organs at each time point exhibited inflammatory injuries to varying degrees after SAH, which reached a maximum at 24-36 h. Incidences of systemic inflammatory response syndrome and MODS were 100 and 71.67%, respectively, after SAH. There is a consistency between MVZ protein expression and inflammatory changes in each organ after SAH. This prompts the suggestion that the MVZ may be one of the direct regulative centers in SAH-induced MODS, and may be involved in the functional regulation of the surrounding organs after SAH.

Chemokine Receptor 7 Implications of Spleen Dendritic Cells in Multiple-organ Dysfunction Syndrome in Mice.

This study aims to explore the chemokine receptor 7 (CCR7) expression of spleen dendritic cells (DCs) and their role in the changes of migration and activity of spleen DCs in multiple-organ dysfunction syndrome (MODS). The MODS model of mice was reproduced. The mice were randomly assigned to the following groups: normal, three-hour to six-hour, 24-hour to 48-hour, and 10-day to 12-day post-zymosan injection. CD11c and CD205 were analysed by immunohistochemistry; the expressions of CD86 and CCR7 of DCs were studied using flow cytometry analyses. In normal mice, many DCs were found at the margin between the red and white pulp. In the three-hour to six-hour and 24-hour to 48-hour group, DC effectively upregulated CD86 and CCR7, and they were distributed in T- cell areas. In the 10-day to 12-day group, DCs were distributed at the margin by the immature form. The CCR7 expression level of DCs had close correlations with the migration of DCs. Chemokine receptor 7 can be used to evaluate the migration and functional activity of DCs in MODS.

Bacterial translocation in an experimental model of multiple organ dysfunctions

BackgroundIn order to investigate the hypothesis that bacterial translocation from the intestine contributes to death after multiple organ dysfunction syndrome (MODS), a sterile MODS model was studied. MethodsMODS was induced in 139 male C57BL/6 mice by lipopolysaccharide (LPS) (endotoxin) infusion followed by zymozan infusion in four groups: Α, sham-operation; Β, LPS; C, LPS + 0.8 g/kg zymozan; and D, LPS + 1.2 g/kg zymozan. Mice were sacrificed at 24 and 48 h for quantitative tissue cultures, isolation, and stimulation of splenocytes, measurement of apoptosis of lymphocytes and macrophages, and of serum LPS and survival. Some mice with MODS were treated with the antibiotic ertapenem. ResultsEnterobacteriaceae and Enterococcus spp were isolated from tissues. Group D had the highest bacterial load and the shortest survival. Release of interleukin-10, of interleukin-17, and of intgerferon-γ by splenocytes and the rate of apoptosis did not concur with immune paralysis. Serum LPS concentrations were higher in mice with MODS versus controls. Ertapenem prolonged survival and decreased the bacterial load. ConclusionsBacterial translocation seems to be an important contributor leading from MODS to death and suggests a change in therapy towards adaptation of antimicrobial treatment upon early signs of MODS.

Observation of extracellular matrix damage in the kidney of rats with multiple organ dysfunction syndrome

Objective To determine the levels of type Ⅳ collagen and matrix metalloproteinase-9 ( MMP-9 ) in the serum and kidney of rats with the multiple organ dysfunction syndrome ( MODS ) and investigate the mechanism of extracellular matrix damage in renal failure of MODS.Methods Forty adult male Sprague- Dawley (SD) rats were randomly (ramdom number) divided into two groups,namely the normal control group ( n =8 ) and the MODS model group ( n =32 ).The rats of model group were further divided into four sub-groups as per different intervals,6 h,12 h,24 h and 48 h,after modeling (n =8 in each).The animal models of MODS were established by two hits,the left eyeball of each model rat was removed to bleed to 2 ml bloocd/100 g body weight and lipopolysaccharide ( LPS,5 mg/kg) was injected into intraperitoneal cavity of model rats four hours later. The same volume of saline instead was injected intraperitoneally into rats of control group.All rats were sacrificed at different intervals.Creatinine (Cr)and blood urea nitrogen (BUN) were determined by using a Hitachi Automatic Biochemical Analyzer.The histological changes in renal tissue were observed under light microscope and transmission electronic microscope.The levels of serum type Ⅳ collagen and MMP - 9 protein were measured by using enzyme linked immunosorbent assay (ELISA).Type Ⅳ collagen and MMP- 9 protein levels in renal tissue were detected by western blot.One - way ANOVA was used for comparison among multiple groups.Results Compared with the control group,Cr and BUN were significantly higher in MODS group ( P ＜0.05 ).There were no histopathological changes in kidney of rats in control group,and the renal injury was serious in rats with MODS.The remarkable edema of basement membrane and defect of collagen fibers in renal tissue were observed in MODS group.Compared with the control group,the levels of MMP-9 in serum increased 6-48 hours after modeling and peaking at interval of 12 hours after modeling ( P ＜ 0.05 ).The protein levels of type Ⅳ collagen increased not significantly in 6 h group and 12 h group in comparison with control group (P ＞ 0.05 ),while those in 24 h group and 48 h group significantly increased ( P ＜ 0.01 ).The levels of MMP -9 in renal tissue of rats with MODS increased in 6 h group and 12 h group (P＜0.05),peaked in 24 h group ( P ＜ 0.05 ),and decreased in 48 hours.However,the level of Ⅳ collagen in serum of rats with MODS decreased significantly 6-48 hours after modeling (P ＜ 0.05 ) Conclusions The injury of extracellular matrix is an important factor to the kidney damage in MODS and it may he used for early diagnose and as a treatment target for kidney injury in MODS. Key words: Multiple organ dysfunction syndrome; Matrixmetalloproteinase-9; Endothelial cell; Extracellular matrix; Collagen Ⅳ; Lipopolysaccharide; Systemic inflammatory response syndrome; Two hits; Rat

Continuous veno-venous hemodiafiltration alleviates multiple organ dysfunction syndrome in dogs

Context: Multiple organ dysfunction syndrome (MODS) is a major cause of death in critically patients. It has been hypothesized that inactivation or removal of pro-inflammatory molecules may prevent or reverse MODS.Objective: The purpose of this paper was to investigate the efficacy of continuous veno-venous hemodiafiltration (CVVHDF) as treatment for MODS in an established animal model.Materials and methods: Male Beagle dogs (n = 18) were used to establish the model and were randomly assigned to a CVVHDF, sham, or control group. The serum levels of ALT, AST, Cr, BUN, PaO2, and PaCO2 were measured as functional makers of major organs. Apoptosis, DLA-DR expression, and cytokine levels of peripheral monocytes were determined.Results: The MODS model was successfully established. After CVVHDF treatment, the WBC and neutrophil counts were lower and the monocyte count and percentage were greater, but these were unchanged in the sham and control groups. Apoptosis of CD14+ monocytes was significantly lower in the CVVHDF group than in the sham and control groups. The fraction of DLA-DR+ monocytes and IL-1β secretion was significantly greater in the sham and control groups than in the CVVHDF group. Moreover, IL-4 secretion increased significantly in the CVVHDF group but not in the control group.Discussion and Conclusion: Our study of an experimental model of MODS indicated that MODS leads to significant disruption of physiological and immune functions. CVVHDF treatment alleviated some of these symptoms due to the improvement of monocyte function, reduction of monocyte apoptosis, and increase of anti-inflammatory cytokines.

Matrix metalloproteinase-9 as new biomarkers of severity in multiple organ dysfunction syndrome caused by trauma and infection

Multiple organ dysfunction syndrome (MODS) is an important cause of morbidity and mortality in intensive care unit. A severe insult in the form of infection or trauma primes the host immune system so that a subsequent, relatively trivial insult produces systemic inflammation response syndrome, which can lead to MODS and death. Matrix metalloproteinase-9 (MMP-9) is stored in the tertiary granules of polymorphonuclear leukocytes. These cells are key effectors in acute inflammatory diseases, such as sepsis and MODS. Endotoxin leads to rapid release of MMP-9 from these granules in vitro and in vivo. However, the role of this enzyme in MODS, and whether it is associated with organ injury at the early stage of MODS remains unclear. This present work may study role of MMP-9 with the MODS rats that caused by trauma and infection and investigate the mechanism of organ injury at the early stage of MODS. Here, we developed a rat model for MODS caused by trauma and infection and analyzed the dynamic level of MMP-9 and determined the relationship between MMP-9 level and early phase of organ injury in MODS rat. The histological changes in pulmonary, renal, and hepatic tissue were observed by light microscope. The expressions of plasma MMP-9 proteins were detected by an enzyme linked immunosorbent assay and its levels in the pulmonary, renal, and hepatic tissue were detected by using immunohistochemistry, respectively. The results indicated that there were no significant improvements in histopathology of rats in control group. However, the pulmonary, renal, and hepatic damage were serious in MODS groups. The concentration of MMP-9 in plasma and tissues of MODS rats increased markedly at the early stage and were higher than that of the control group. Moreover, the MMP-9 level in plasma positively correlated with the levels of pulmonary, renal, and hepatic tissue. This study clearly shows that MMP-9 is good biomarker to predict the severity of injury organ at the early phase of MODS.

The immune function influence of the CD4 + T helper cell after the treatment of continuous blood purification in a porcine model with multiple organ dysfunction syndrome

Objective To investigate the levels of Th1 and Th2 cell in the peripheral and the cytokines (IFN-γ,TNF-α,IL-12,IL-10,IL-4) in the culture medium at different time in the porcine model with multiple organ dysfunction syndrome(MODS) after continuous blood purification(CBP). Methods Twenty-four young porcines were given intravenous infusion of endotoxin to induce MODS, then were randomly divided into 2 groups:CBP group(n = 12) and MODS group without CBP(n = 12). Continuous venovenous hemodiafiltration (CVVHDF) was the main mode for CBP. At baseline, onset of MODS, and 2 h,4 h,6 h after treatment of CVVHDF,we picked the blood respectively to separate the T helper cell using the beads,detected the Th1 and Th2 cell by FACS and detected the cytokines (IFN-γ,TNF-α,IL-12,IL-10,IL-4) in the culture medium by ELISA. Results The MODS group showed a obvious rise in TNF-α,the drop tendency in IL-12,IFN-γ,IL-10,Th1/Th2 ratio, and no significant change in IL-4. After the treatment, the CBP group showed the drop in TNF-α and IL-4;and increase in IL-12,IFN-γ,IL-10 and Th1/Th2 ratio. Conclusion CBP helps to dear immune function,and restore the balance of Th1/Th2 in porcine MODS model. Key words: MODS; Th1/Th2; Continuous blood purification; Porcine model