Hemorrhagic Shock-reperfusion Research Articles

Long period changes of hippocampal diffusion kurtosis imaging and its correlation with cognitive dysfunction after incomplete cerebral ischemia-reperfusion in rats.

This study aims to summarize the changes of functional diffusion kurtosis imaging (DKI) parameters in the bilateral hippocampal CA1 region of the hemorrhagic shock reperfusion (HSR) model of rats and their correlation with cognitive dysfunction. Adult male Sprague-Dawley rats (9-10weeks of age, weighing 350-400g) were randomized into the HSR group (n = 30) and the sham-operated group (Sham) (n = 30). Rats in the HSR group and the Sham group were subdivided into five time points (1, 2, 4, 8, and 12weeks) for examination. Diffusion kurtosis imaging (DKI) was performed. Cognitive dysfunction was analyzed by the Morris Water Maze. The correlation between the DKI parameters and cognitive dysfunction was analyzed by the Spearman correlation. In the HSR group, the values of axial kurtosis (Ka), radial kurtosis (Kr), and mean kurtosis (MK) in the bilateral hippocampal CA1 of rats at 1, 2, 4, 8 and 12weeks after the surgery were significantly higher. The rats in the HSR group had significantly longer escape latency than in the Sham group. The rats in the HSR group had significantly shorter time and shorter distance in target quadrant than those in the Sham group. The escape latency had positive correlation with MK, Ka, and Kr. The distance and the time in target quadrant had negative correlation with MK, Ka, and Kr. The parameters get from the DKI could accurately evaluate the abnormal blood perfusion and microstructure changes in hippocampal CA1 area of the incomplete cerebral ischemia reperfusion rats induced by HSR. MK, Ka, and Kr values could reflect the decreased learning and memory ability in HSR rat model.

Long period changes of hippocampal cerebral blood flow and its correlation with anxiety-like behavior and inflammation after incomplete cerebral ischemia reperfusion in rats.

This study was designed to summarize the changes of cerebral blood flow (CBF) in the bilateral hippocampal CA1 region of the hemorrhagic shock reperfusion (HSR) model of rats and their correlation with anxiety-like behavior and inflammation. Rats were randomly divided into the HSR group and the Sham group. 30 rats in each group were subdivided into 5 time points (1 w, 2 w, 4 w, 8 w, and 12 w) for examination. 3D-arterial spin labeling (3D-ASL) was performed. Long period anxiety-like behaviors were analyzed through the open field test. Histopathology was used to detect astrocytic activation in bilateral hippocampus. The concentrations of pro-inflammatory cytokines were analyzed by ELISA. At 1, 2, 4, and 8 weeks, CBF in bilateral hippocampus CA1 area of the rats in the Sham group was significantly higher than the rats in the HSR group. The rats in the HSR group had significantly shorter total traveled distance, lower velocity, and less rearing counts than those in the Sham group at 1, 2, 4, 8, and 12 weeks after the surgery. The CBF at 1, 2, 4, 8, and 12 weeks after the surgery had positive correlation with the total traveled distance, velocity, and rearing counts in the open field test. The rats in the HSR group had significantly higher GFAP intensity and the concentrations of IL-6, IL-1β, and TNF-α than those in the Sham group at 1, 2, 4, 8, and 12 weeks after the surgery. The CBF at 1, 2, 4, 8 and 12 weeks after the surgery had significantly negative correlation with the GFAP intensity and the concentrations of IL-6, IL-1β, and TNF-α. In conclusion, CBF in bilateral hippocampus CA1 area, spatial exploration ability in rats with HSR were decreased while the astrocyte activation was enhanced. During the long period after the induction of HSR, the value of CBF in bilateral hippocampus CA1 area was proved to have significant correlation with anxiety-like behaviors and astrocyte activation.

Advanced MRI to assess hippocampal injury after incomplete cerebral ischemia-reperfusion in rats.

The purpose of this study was to evaluate advanced MRI findings in the bilateral hippocampus CA1 region of rats with hemorrhagic shock reperfusion (HSR) and their correlation with histopathological results. Additionally, this study aimed to identify effective MRI examination methods and detection indexes for assessing HSR. Rats were randomized into the HSR and the Sham groups with 24 rats in each group. MRI examination included diffusion kurtosis imaging (DKI) and 3-dimensional arterial spin labeling (3D-ASL). Apoptosis and pyroptosis were evaluated directly from tissue. In the HSR group, cerebral blood flow (CBF) was significantly lower than that of the Sham group, while radial kurtosis (Kr), axial kurtosis (Ka), and mean kurtosis (MK) were all higher. In the HSR group, fractional anisotropy (FA) at 12 and 24hours and radial diffusivity, axial diffusivity (Da), and mean diffusivity (MD) at 3 and 6hours were lower than in the Sham group. MD and Da at 24hours in the HSR group were significantly higher. The apoptosis rate and pyroptosis rate were also enhanced in the HSR group. CBF, FA, MK, Ka, and Kr values in the early stage were strongly correlated with apoptosis rate and pyroptosis rate. The metrics were obtained from DKI and 3D-ASL. Advanced MRI metrics from DKI and 3D-ASL, including CBF, FA, Ka, Kr, and MK values, are useful to evaluate abnormal blood perfusion and microstructural changes in the hippocampus CA1 area in the setting of incomplete cerebral ischemia-reperfusion in rats induced by HSR.

ER stress preconditioning ameliorates liver damage after hemorrhagic shock and reperfusion.

The mismatch of oxygen supply and demand during hemorrhagic shock disturbs endoplasmic reticulum (ER) homeostasis. The resulting accumulation of unfolded proteins in the ER lumen, which is a condition that is defined as ER stress, triggers the unfolded protein response (UPR). Since the UPR influences the extent of organ damage following hemorrhagic shock/reperfusion (HS/R) and mediates the protective effects of stress preconditioning before ischemia-reperfusion injury, the current study investigated the mechanisms of ER stress preconditioning and its impact on post-hemorrhagic liver damage. Male C56BL/6-mice were injected intraperitoneally with the ER stress inductor tunicamycin (TM) or its drug vehicle 48 h prior to being subjected to a 90 min pressure-controlled hemorrhagic shock (30±5 mmHg). A period of 14 h after hemorrhagic shock induction, mice were sacrificed. Hepatocellular damage was quantified by analyzing hepatic transaminases and hematoxylin-eosin stained liver tissue sections. Additionally, the topographic expression patterns of the ER stress marker binding immunoglobulin protein (BiP), UPR signaling pathways, and the autophagy marker Beclin1 were evaluated. TM injection significantly increased BiP expression and modified the topographic expression patterns of the UPR signaling proteins. In addition, immunohistochemical analysis of Beclin1 revealed an increased pericentral staining intensity following TM pretreatment. The histologic analysis of hepatocellular damage demonstrated a significant reduction in cell death areas in HS/R+TM (P=0.024). ER stress preconditioning influences the UPR and alleviates post-hemorrhagic liver damage. The beneficial effects were, at least partially, mediated by the upregulation of BiP and autophagy induction. These results underscore the importance of the UPR in the context of HS/R and may help identify novel therapeutic targets.

Protective effect of the total flavonoids of drynariae on renal reperfusion injury after hemorrhagic shock

Objective To investigate the protective effect of total flavonoids of drynaria on hemorrhagic shock reperfusion renal injury. Methods The 30 Sprague-Dawley rats were randomly divided into 3 groups: sham operation group, experimental group (hemorrhagic shock group) and drynaria fortunei group, 10 in each group. In drynaria fortunei group and experiment group, the blood from the femoral artery was withdrawn until the mean arterial pressure reached 40 mmHg in 90 min, and then the withdrawn blood transfusion were reinfused and blood pressure recovered to the base value of 90%. The rats of drynaria fortunei group were given intraperitoneal injection of Drynaria total flavonoid 300 mg/kg, and experimental group and sham operation group were injected with 3 ml physiological saline. Blood creatinine (SCr) levels, the renal cell apoptosis index, the expression of Bcl-2 and mRNA Bax in kidney were detected. Results Compared with the experimental group, serum SCr (78.36 ± 5.31 mmol/L vs. 151.43 ± 11.8 mmol/L) of drynaria fortunei group decreased significantly (P<0.01); the renal cell apoptosis (19.56% ± 4.37% vs. 14.31% ± 2.83%), the expression level of Osteopractic rats of Bax group mRNA (1.24 ± 0.05 vs. 0.91 ± 0.07) of drynaria fortunei group decreased significantly; and the Bcl-2 mRNA (0.65 ± 0.05 vs. 1.38 ± 0.07) and the expression level and Bcl-2/bax ratio (0.52 ± 0.06 vs. 1.51 ± 0.08) of drynaria fortunei group increased significantly (P<0.01). Conclusions The drynaria total flavonoids on rats with hemorrhagic shock and resuscitation of renal injury has a protective effect, and its mechanism may improve the expression of Bcl-2 and mRNA, increase the ratio of bcl-2/bax, and inhibit or block the apoptosis of renal tissue. Key words: Kidney; Shock, hemorrhagic; Reperfusion injury; Drynaria total flavonoid; Apoptosis; Genes, bcl-2; Rats

Elevation of jugular venous superoxide anion radical is associated with early inflammation, oxidative stress, and endothelial injury in forebrain ischemia–reperfusion rats

A novel electrochemical sensor was used in this study to determine the correlations between jugular venous O2− and HMGB1, malondialdehyde (MDA), and intercellular adhesion molecule-1 (ICAM-1) in rats with forebrain ischemia/reperfusion (FBI/R). Twenty-one male rats were divided into a Sham group, a hemorrhagic shock/reperfusion (HS/R) group, and a forebrain ischemia/reperfusion (FBI/R) group. The O2− sensor in the jugular vein detected the current derived from O2− generation (abbreviated as “O2− current”), which was integrated as the partial value of quantified electricity during ischemia (QI) and after reperfusion (QR). The plasma O2− current showed a gradual increase during forebrain ischemia in the HS/R and the FBI/R groups. The current showed a marked increase immediately after reperfusion and continued for more than 60 min in the FBI/R group. In the HS/R group, the current was gradually attenuated to the baseline level. Brain and plasma HMGB1 increased significantly in the FBI/R group compared with those in the Sham and the HS/R groups, and both brain and plasma HMGB1 correlated significantly with the sum of QI and QR (total Q). Brain and plasma MDA and plasma soluble ICAM-1 also correlated significantly with total Q. Here, we report the correlation between O2− and HMGB1, MDA, and sICAM-1 in rats with cerebral ischemia–reperfusion, using a novel electrochemical sensor. These data indicated that excessive production of O2− after ischemia–reperfusion was associated with early inflammation, oxidative stress, and endothelial activation in the brain and plasma, which might enhance the ischemia–reperfusion injury.

Effect of Astragalus membranaceus injection on the activity of the intestinal mucosal mast cells after hemorrhagic shock-reperfusion in rats

The mechanism of mucosal damage induced by ischemia-reperfusion (IR) after hemorrhagic shock is complex; mast cells (MC) degranulation is associated with the mucosal damage. Astragalus membranaceus can protect intestinal mucosa against intestinal oxidative damage after hemorrhagic shock, and some antioxidant agents could prevent MC against degranulation. This study aimed to observe the effects of astragalus membranaceus injection on the activity of intestinal mucosal mast cells (IMMC) after hemorrhage shock-reperfusion in rats. Thirty-two Wistar rats were randomly divided into the normal group, model group, low dosage group, (treated with Astragalus membranacaus injection, 10 g crude medication/kg) and high dosage group (treated with Astragalus membranacaus injection, 20 g crude medication/kg). The rat model of hemorrhagic shock-reperfusion was induced by hemorrhage for 60 minutes followed by 90 minutes of reperfusion. The animals were administrated with 3 ml of the test drug solution before reperfusion. At the end of study, intestinal pathology, ultrastructure of IMMC, and expression of tryptase were assayed. The levels of malondisldehyde (MDA), TNF-alpha, histamine, and superoxide dismutase (SOD) activity in intestine were detected, and the number of IMMC was counted. The Chiu's score of the rats in the model group was higher than in other groups (P < 0.01). The Chiu's score in the high dosage group was higher than that in the low dosage group (P < 0.05). Hemorrhage-reperfusion induced IMMC degranulation: Astragalus membranaceus injection attenuated this degranulation. Expression of tryptase and the number of IMMC in the model group increased compared with the other groups (P < 0.01) and was significantly reduced by the treatments of Astragalus membranaceus injection at both doses. There was no significant difference between the two treatment groups (P > 0.05). MDA content and concentration of TNF-alpha in the model group were higher than that in the other three groups (P < 0.05), and the concentration of TNF-alpha in the low dosage group was higher than that in the high dosage group (P < 0.05). SOD activity and the concentration of histamine in the model group were lower than the other three groups (P < 0.05). There was a negative correlation between the Chiu's score and the concentration of histamine and a positive correlation between the Chiu's score and the concentration of TNF-alpha and between the SOD activity and the concentration of histamine in the four groups (P < 0.05). Astragalus membranaceus injection may reduce the damage to small intestine mucosa by inhibiting the activated IMMC after hemorrhagic shock.

LEUKOCYTE-ENDOTHELIUM INTERACTIONS AFTER HEMORRHAGIC SHOCK/REPERFUSION AND CECAL LIGATION/PUNCTURE

Hemorrhagic shock/reperfusion (HS/R) followed by sepsis triggers systemic microcirculatory disturbances that may induce multiple organ failure. The present study evaluated the effects of HS/R and cecal ligation and puncture, followed by necrotic cecal resection/peritoneal lavage (REL) on leukocyte-endothelium interactions at the mesentery. Eighty-one anesthetized Wistar rats (200-250 g) were randomly assigned to a first injury: (1) control-HS-no hemorrhagic shock/no reperfusion group, (2) HS/blood-HS/R with 25% shed blood, and (3) HS/blood + LR-HS/R with 25% of the shed blood + lactated Ringer's solution, 3x shed blood volume. Twenty-four hours post-HS/R, animals were submitted to cecal ligation and puncture and, 24 h thereafter, to REL. Leukocyte-endothelium interactions were assessed by intravital microscopy and intercellular adhesion molecule (ICAM) 1 and P-selectin expression by immunohistochemistry. Lungs were observed for ICAM-1 expression and neutrophil infiltration. Single and double injury induced significant increases in rolling (approximately 2-fold), adherent (approximately 5-fold), and migrated leukocytes (approximately 7-fold); ICAM-1 expression (approximately 1/2-fold), and P-selectin expression (approximately 1/2-fold) at the mesentery compared with control-HS group. REL normalized leukocyte-endothelium interactions at the mesentery in single-injured animals. However, in double-injured rats, adherence and migration of leukocytes decreased but did not normalize. Similar results were observed on ICAM-1 expression and neutrophil infiltration in the lungs from these animals. In conclusion, the current in vivo observation of the mesenteric microcirculation after a double injury followed by REL is a suitable model for the systematic evaluation of the inflammatory reaction at local and distant sites. In addition, data presented herein emphasized the importance of surgical removal of the septic focus in controlling the otherwise lethal sepsis-induced multiple organ dysfunction syndrome.

Protective effect ofAstragalus membranaceuson intestinal mucosa reperfusion injury after hemorrhagic shock in rats

To study the protective effect of Astragalus membranaceus on intestinal mucosa reperfusion injury and its mechanism after hemorrhagic shock in rats. A total of 32 SD rats were randomly divided into four groups (n = 8, each group): normal group, model group, low dosage group (treated with 10 g/kg Astragalus membranaceus) and high dosage group (treated with 20 g/kg Astragalus membranaceus). The model of hemorrhagic shock for 60 min and reperfusion for 90 min was established. Therapeutic solution (3 mL) was administrated before reperfusion. At the end of the study, the observed intestinal pathology was analyzed. The blood concentrations of lactic acid (LD), nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) in intestinal mucosa were determined. The intestinal mucosa pathology showed severe damage in model group and low dosage group, slight damage in high dosage group and no obvious damage in normal group. The Chiu's score in low dose group and high dose group was significantly lower than that in model group. The content of MDA in model group was higher than that in low and high dose groups, while that in high dose group was almost the same as in normal group. The activity of SOD and GSH-PX was the lowest in model group and significantly higher in high dose group than in normal and low dose groups. The concentrations of LD and ET-1 in model group were the highest. The concentrations of NO in model group and low dose group were significantly lower than those in high dose group and normal group. High dose Astragalus membranaeus has much better protective effect on hemorrhagic shock-reperfusion injury of intestinal mucosa than low dose Astragalus membranaceus. The mechanism may be that Astragalus membranaceus can improve antioxidative effect and regulate NO/ET level during hemorrhagic reperfusion.

Effects of extract F of red-rooted Salvia on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock-reperfusion in rats.

To compare the effects of extract F of red-rooted Salvia (EFRRS) on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock and reperfusion in rats. The rats were subject to hemorrhagic shock and followed by reperfusion, and were divided randomly into two groups. Group 1 received saline, and group 2 received EFRRS intravenously. The index of gastric mucosal lesions (IGML) was expressed as the percentage of lesional area in the corpus or antrum. The degree of gastric mucosal lesions (DGML) was catalogued grade 0,1,2 and 3. The concentrations of prostaglandins (PGs) were measured by radioimmunoassay. The concentration of MDA was measured according to the procedures of Asakawa. The activity of SOD was measured by the biochemical way. The growth rates or inhibitory rates of above-mentioned parameters were calculated. As compared with IGML (%), grade 3 damage (%) and MDA content (nmol/g tissue) of gastric antrum which were respectively 7.96 +/- 0.59, 34.86 +/- 4.96 and 156.98 +/- 16.12, those of gastric corpus which were respectively 23.18 +/- 6.82, 58.44 +/- 9.07 and 230.56 +/- 19.37 increased markedly (P <0.01), whereas the grade 0 damage, grade 1 damage, the concentrations of PGE(2) and PGI(2)(pg/mg tissue), the ratio of PGI(2)/TXA(2) and the activity of SOD (U/g tissue) of corpus which were respectively 3.01 +/- 1.01, 8.35 +/- 1.95, 540.48 +/- 182.78, 714.38 +/- 123.74, 17.38 +/- 5.93 and 134.29 +/- 13.35 were markedly lower than those of antrum which were respectively 13.92 +/- 2.25, 26.78 +/- 6.06, 2218.56 +/- 433.12, 2531.76 +/- 492.35, 43.46 +/- 8.51 and 187.45 +/- 17.67 (P<0.01) after hemorrhagic shock and reperfusion. After intravenous EFRRS, the growth rates (%) of grade 0 damage, grade 1 damage, the concentrations of PGE(2) and PGI(2), the ratio of PGI(2)/TXA(2) and the activity of SOD of corpus which were respectively 632.56, 308.62, 40.75, 74.75, 92.29 and 122.25 were higher than those in antrum which were respectively 104.89, 58.40, 11.12, 56.58, 30.65 and 82.64, whereas the inhibitory rates (%) of IGML, grade 3 damage and MDA content of gastric corpus were 82.93, 65.32 and 59.09, being higher than those of gastric antrum which were 76.64, 53.18 and 42.37. After hemorrhagic shock reperfusion, the gastric mucosal lesions in the corpus were more severe than those in the antrum, which were related not only to the different distribution of endogenous PGs in the mucosa, but also to the different ability of anti-oxidation of the mucosa. The protective effect of EFRRS on the gastric mucosa in the corpus was more evident than that in the antrum, which was related to higher growth degree of PGs contents and anti-oxitative ability in gastric corpus after administration of EFRRS.

Effects of extract F of red-rooted Salvia on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock-reperfusion in rats

Effects of extract F of red-rooted Salvia on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock-reperfusion in rats

Effects of extract F of red-rooted Salvia on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock-reperfusion in rats

Effects of extract F of red-rooted Salvia on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock-reperfusion in rats

Effects of proton pump inhibitor on gastric mucosa hemodynamics and tissue oxygenation in anesthetized rats

Proton pump inhibitors have been reported to have a cytoprotective action in addition to the anti-secretory action of acid. The precise mechanism, however, remains obscure. In this study, the effects of proton pump inhibitors (omeprazole and NC-1300) on gastric mucosa hemodynamics and tissue oxygenation were investigated using organ reflectance spectrophotometry in a hemorrhagic shock-reperfusion model involving anesthetized rats. Neither drug affected gastric mucosa hemodynamics nor tissue oxygenation in the basal state before hemorrhage. During the shock state, however, these drugs maintained tissue oxygenation and reduced ulcer formation, although they did not show a significant effect on gastric mucosa blood volume. The results suggest that both proton pump inhibitors have an anti-ulcer action by maintaining mucosal oxygenation in addition to the anti-secretory activity of acid.

The effect of DQ-2511, a newly synthesized anti-ulcer drug, on the gastric mucosal hemodynamics and ulceration in rats.

DQ-2511, which is a dopamine derivative, is a newly synthesized anti-ulcer drug. Pretreatment with DW-2511 in the hemorrhagic shock-reperfusion model in rats significantly prevented the decreases of gastric mucosal blood volume, mucosal blood oxygenation index and the ulcer formation. The decrease in gastric mucosal blood oxygenation index in hemorrhagic shock state has a linear correlation with the size of the mucosal ulcers both in DQ-2511 and control groups. The results suggested that DQ-2511 exerts its anti-ulcer activity by improving mucosal hemodynamics in hemorrhagic shock-reperfusion rat model.