Obstruction In Rats Research Articles

Expression of the HIF-1α/VEGF pathway is upregulated to protect alveolar bone density reduction in nasal-obstructed rats.

Hypoxia and mouth breathing are closely related to maxillofacial bone metabolism and are characteristic of obstructive sleep apnea-hypopnea syndrome (OSAHS). Being key factors in the hypoxia response, hypoxia-inducible factor 1α (HIF-1α) and HIF-responsive gene vascular endothelial growth factor (VEGF) are essential for bone remodeling. This study focuses on the role of the HIF-1α/VEGF pathway in alveolar bone metabolism during OSAHS. 36 three-week-old male Wistar rats were divided into three groups: twelve control rats, twelve bilateral nasal obstructed (BNO) rats, twelve BNO rats treated with intraperitoneal injection of Dimethyloxalylglycine (DMOG). After two weeks, the microstructure and bone mineral density (BMD) of alveolar bone were evaluated using micro-computed tomography (micro-CT). The expressions of HIF-1α and VEGF in the alveolar bone were then assessed via immunohistochemistry staining, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Alkaline phosphatase (ALP) staining and Alizarin red S staining were performed to evaluate osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs). Significant reductions in alveolar bone density were noted in BNO rats. Bilateral nasal obstruction increased the expressions of HIF-1α and VEGF in alveolar bone. With upregulation of HIF-1α/VEGF via DMOG, alveolar bone density of BNO rats increased. Furthermore, DMOG promoted the osteogenic differentiation of BMSCs by stabilizing the HIF-1α protein and increasing the expression of VEGF. Bilateral nasal obstruction changes alveolar bone structure and leads to a reduction in alveolar bone density. Moreover, the expression of the HIF-1α/VEGF signaling pathway increases to protect alveolar bone density reduction in BNO rats.

Local Injection of Stem Cells Can Be a Potential Strategy to Improve Bladder Dysfunction after Outlet Obstruction in Rats.

This study investigates whether hAFSCs can improve bladder function in partial bladder outlet obstruction (pBOO) rats by targeting specific cellular pathways. Thirty-six female rats were divided into sham and pBOO groups with and without hAFSCs single injection into the bladder wall. Cystometry, inflammation/hypoxia, collagen/fibrosis/gap junction proteins, and smooth muscle myosin/muscarinic receptors were examined at 2 and 6 weeks after pBOO or sham operation. In pBOO bladders, significant increases in peak voiding pressure and residual volume stimulated a significant upregulation of inflammatory and hypoxic factors, TGF-β1 and Smad2/3. Collagen deposition proteins, collagen 1 and 3, were significantly increased, but bladder fibrosis markers, caveolin 1 and 3, were significantly decreased. Gap junction intercellular communication protein, connexin 43, was significantly increased, but the number of caveolae was significantly decreased. Markers for the smooth muscle phenotype, myosin heavy chain 11 and guanylate-dependent protein kinase, as well as M2 muscarinic receptors, were significantly increased in cultured detrusor cells. However, hAFSCs treatment could significantly ameliorate bladder dysfunction by inactivating the TGFβ-Smad signaling pathway, reducing collagen deposition, disrupting gap junctional intercellular communication, and modifying the expressions of smooth muscle myosin and caveolae/caveolin proteins. The results support the potential value of hAFSCs-based treatment of bladder dysfunction in BOO patients.

Combination of Honey and Nigella sativa Oil Reduce Oxidative Stress and Inflammation in Unilateral Ureteral Obstruction in Rats

Combination of Honey and Nigella sativa Oil Reduce Oxidative Stress and Inflammation in Unilateral Ureteral Obstruction in Rats

Contralateral renal change in a unilateral ureteral obstruction rat model using intravoxel incoherent motion diffusion-weighted imaging

Objectives Most functional magnetic resonance research has primarily examined alterations in the affected kidney, often neglecting the contralateral kidney. Our study aims to investigate whether imaging parameters accurately depict changes in both the renal cortex and medulla in a unilateral ureteral obstruction rat model, thereby showcasing the utility of intravoxel incoherent motion (IVIM) in evaluating contralateral renal changes. Methods Six rats underwent MR scans and were subsequently sacrificed for baseline histological examination. Following the induction of left ureteral obstruction, 48 rats were scanned, and the histopathological examinations were conducted on days 3, 7, 10, 14, 21, 28, 35, and 42. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudodiffusion (D*), and perfusion fraction (f) values were measured using IVIM. Results On the 10th day of obstruction, both cortical and medullary ADC values differed significantly between the UUO10 group and the sham group (p < 0.01). The cortical D values showed statistically significant differences between UUO3 group and sham group (p < 0.01) but not among UUO groups at other time point. Additionally, the cortical and medullary f values were statistically significant between the UUO21 group and the sham group (p < 0.01). Especially, the cortical f values exhibited significant differences between the UUO21 group and the UUO groups with shorter obstruction time (at time point of 3, 7, 10, 14 day) (p < 0.01). Conclusions Significant hemodynamic alterations were observed in the contralateral kidney following renal obstruction. IVIM accurately captures changes in the unobstructed kidney. Particularly, the cortical f value exhibits the highest potential for assessing contralateral renal modifications.

Huoxue Jiedu Huayu recipe inhibits macrophage-secreted vascular endothelial growth factor-a on angiogenesis and alleviates renal fibrosis in the contralateral kidneys of unilateral ureteral obstruction rats.

Male Wistar rats were randomly divided into 4 groups: the sham group, UUO group (180 d of left ureter ligation), UUO plus eplerenone (EPL) group, and UUO plus HJHR group. After 180 d of oral drug administration, blood and contralateral kidneys were collected for analysis. Angiogenesis- and fibrosis-related indexes were detected. HJHR and EPL improved structural damage and renal interstitial fibrosis in the contralateral kidney and reduced the protein expression levels of α-smooth muscle actin (α-SMA), vimentin and collagen I. Moreover, these treatments could reduce the expression of vascular endothelial growth factor-A (VEGFA) by inhibiting the infiltration of macrophages. Furthermore, HJHR and EPL significantly reduced the expression of CD34 and CD105 by downregulating VEGFA production, which inhibited angiogenesis. Finally, the coexpressions of CD34, CD105 and α-SMA were decreased in the HJHR and EPL groups, indicating that endothelial-to-mesenchymal transition was inhibited. These findings confirm that HJHR alleviates contralateral renal fibrosis by inhibiting VEGFA-induced angiogenesis, encourage the use of HJHR against renal interstitial fibrosis and provide a theoretical basis for the clinical management of patients with CKD.

Fluorofenidone attenuates renal fibrosis by inhibiting lysosomal cathepsin‑mediated NLRP3 inflammasome activation.

Currently, no antifibrotic drug in clinical use can effectively treat renal fibrosis. Fluorofenidone (AKFPD), a novel pyridone agent, significantly reduces renal fibrosis by inhibiting the activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome; however, the underlying mechanism of this inhibition is not fully understood. The present study aimed to reveal the molecular mechanism underlying the suppression of NLRP3 inflammasome activation by AKFPD. It investigated the effect of AKFPD on NLRP3 activation and lysosomal cathepsins in a unilateral ureteral obstruction (UUO) rat model, and hypoxia/reoxygenation (H/R)-treated HK-2 cells and murine peritoneal-derived macrophages (PDMs) stimulated with lipopolysaccharide (LPS) and ATP. The results confirmed that AKFPD suppressed renal interstitial fibrosis and inflammation by inhibiting NLRP3 inflammasome activation in UUO rat kidney tissues. In addition, AKFPD reduced the production of activated caspase-1 and maturation of IL-1β by suppressing NLRP3 inflammasome activation in H/R-treated HK-2 cells and murine PDMs stimulated with LPS and ATP. AKFPD also decreased the activities of cathepsins B, L and S both in vivo and in vitro. Notably, AKFPD downregulated cathepsin B expression and NLRP3 colocalization in the cytoplasm after lysosomal disruptions. Overall, the results suggested that AKFPD attenuates renal fibrosis by inhibiting lysosomal cathepsin-mediated activation of the NLRP3 inflammasome.

Noninvasive Diagnosis of Kidney Dysfunction Using a Small-Molecule Manganese-Based Magnetic Resonance Imaging Probe.

Contrast-enhanced magnetic resonance imaging (CE-MRI) is a promising approach for the diagnosis of kidney diseases. However, safety concerns, including nephrogenic systemic fibrosis, limit the administration of gadolinium (Gd)-based contrast agents (GBCAs) in patients who suffer from renal impairment. Meanwhile, nanomaterials meet biosafety concerns because of their long-term retention in the body. Herein, we propose a small-molecule manganese-based imaging probe Mn-PhDTA as an alternative to GBCAs to assess renal insufficiency for the first time. Mn-PhDTA was synthesized via a simple three-step reaction with a total yield of up to 33.6%, and a gram-scale synthesis can be realized. Mn-PhDTA has an r1 relaxivity of 2.72 mM-1 s-1 at 3.0 T and superior kinetic inertness over Gd-DTPA and Mn-EDTA with a dissociation time of 60 min in the presence of excess Zn2+. In vivo and in vitro experiments demonstrate their good stability and biocompatibility. In the unilateral ureteral obstruction rats, Mn-PhDTA provided significant MR signal enhancement, enabled distinguishing structure changes between the normal and damaged kidneys, and evaluated the renal function at different injured stages. Mn-PhDTA could act as a potential MRI contrast agent candidate for the replacement of GBCAs in the early detection of kidney dysfunction and analysis of kidney disease progression.

Abnormal urodynamic changes in post-upper urinary tract dysfunction in ureteral obstruction rat models.

Objects: This study investigated changes in upper urinary tract urodynamics (UUTU) after upper urinary tract dysfunction (UUTD). Methods: The UUTD model was induced through unilateral ureteral obstruction. To measure the renal pelvis volume, and resting pressure. Ureteral electromyography (EMG) and in situ ureteral constriction experiments were performed. Ureteral tissue was obtained for HE and masson staining, IF staining and IHC research to explore the distribution of Piezo1, and the expression of Piezo1 was studied using Western blotting. Results: The study showed that the renal pelvis volumes and the renal pelvis resting pressures gradually increased post surgery in the experimental group. The degree of ureteral tissue edema, cell necrosis and fibrosis gradually increased. The maximum contraction force and frequency of ureter in the experimental group post surgery were significantly higher than in the sham group. Western blotting showed that the expression intensity of Piezo1 gradually increased and was significantly higher than in the sham group. Further analysis of each sub-layer of the ureter revealed that Piezo1 was highly expressed in the urothelium layer, followed by the suburothelium layer, and had low expression in the smooth muscle cell layer. Conclusion: The study observed that morphological and electrophysiological changes in the upper urinary tract may be important mechanisms of abnormal UUTU. Increased expression of the Piezo1 may be a new molecular mechanism of abnormal urodynamics after UUTD.

Is bladder outlet obstruction rat model to induce overactive bladder (OAB) has similarity to human OAB? Research on the events in smooth muscle, collagen, interstitial cell and telocyte distribution

BackgroundCellular and cytoskeletal events of overactive bladder (OAB) have not been sufficiently explored in human bladder due to different limitations. Bladder outlet obstruction (BOO) had been induced in different animal models with different methods to induce (OAB). Similarity of the animal models of BOO to the human OAB is postulated but has not been confirmed. The interstitial cells of Cajal (ICCs), and telocytes (TCs) are an important players in smooth muscles conductivity, they had not been well investigated in the previous BOO models. Objectives are to investigate the morphological pattern of cellular, cytoskeleton and telocytes distribution in BOO rat model and to match the events in two time periods and compare it to the findings in real-world human OAB.MethodsFemale Sprague-Dawley rats (Rattus norvegicus) were randomly divided into: sham (n = 10), BOO 6 W (n = 10), BOO 8 W (n = 10). Operative procedure to Induce BOO was done under anesthesia with intraperitoneal Ketamine administration. The Effect of induction of BOO was evaluated after 6 and 8 weeks. The rats were anesthetized, and the urinary bladder was removed, while the rat was unconscious under anaesthesia it was transferred to the inhalation anaesthesia cage for euthanasia, rats were sacrificed under light anesthesia using isoflurane. Care of animals, surgical procedure, and euthanasia adhered to Guide for the Care and Use of Laboratory Animals, and AVMA Guidelines for the Euthanasia of Animals. The retrieved bladder was processed for examination with histopathology, immunohistochemistry (IHC), and transmission electron microscopy (EM).ResultsHistological examination of the bladder shows thinner urothelium, condensation of collagen between muscle bundles. IHC with c-kit shows the excess distribution of ICCs between smooth muscle bundles. EM shows frequent distribution of TCs that were situated between collagen fibers. Finings in BOO 6 W group and BOO 8 W group were comparable.ConclusionThe animal model study demonstrated increased collagen/ smooth muscle ratio, high intensity of ICCs and presence of TCs. Findings show that a minimally invasive procedure to induce BOO in rats had resulted in an OAB that has morphological changes that were stable in 6 & 8 weeks. We demonstrated the distribution of TCs and ICCs in the rat animal model and defined them. The population of TCs in the BOO rat model is described for the first time, suggests that the TCs and ICCs may contribute to the pathophysiology of OAB. Similarity of animal model to human events OAB was demonstrated. These findings warrant further study to define the role of TCs in OAB.Clinical trial registryThe study does not require a clinical trial registration; it is an experimental animal study in basic science and does not include human subjects.

LncRNA Meg3 Aggravates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Rats by Activating the Hedgehog Pathway.

The hedgehog signaling pathway exerts vital functions in regulating epithelial-to-mesenchymal transition (EMT) in renal interstitial fibrosis (RIF). It was reported that lncRNA-maternally expressed gene 3 (lncRNA Meg3) can regulate hepatic fibrosis by regulating the expression of smoothened (Smo) in the hedgehog signaling pathway. However, the specific role of lncRNA Meg3 in renal fibrosis resulting from unilateral ureteral obstruction (UUO) by regulating the hedgehog signaling pathway has not been reported. Hence, this research aimed to expound the effects of lncRNA Meg3 on renal fibrosis induced by UUO in rats via the hedgehog pathway. Peripheral blood was collected from patients with chronic kidney disease (CKD, CKD group) and healthy volunteers (Normal group) at the same period. In addition, 6-week-old male Sprague-Dawley (SD) rats were divided to Sham, UUO, UUO+shRNA Negative control (shNC), and UUO+sh-Meg3 groups, and their kidney tissues and serum were gathered. Next, quantitative real-time polymerase chain reaction (qRT-PCR) was employed for detecting the lncRNA Meg3 expression level in the serum of patients and renal tissue of rats; kits for testing levels of blood urea nitrogen (BUN), creatinine (Cr), hydroxyproline (HYP), and 24-hour urine protein (24-up) in rats of each group; hematoxylin and eosin (HE) staining and Masson staining for observing kidney tissue and renal fibrosis level in rats; western blot for measuring levels of collagen type III (Col III), α-Smooth muscle actin (α-SMA), fibronectin, E-cadherin, sonic hedgehog (Shh), patched (Ptch) protein, smoothened (Smo) protein and glioma-associated oncogene homolog 1 (Gli1) protein expression. LncRNA Meg3 was highly expressed in CKD patients and UUO rats (p < 0.01). In contrast to the UUO+shNC group, knocking down lncRNA Meg3 improved renal injury, relieved pathological renal lesions, and reduced kidney fibrosis and related protein levels. It inhibited the hedgehog pathway in kidney tissues of UUO rats (p < 0.05 and p < 0.01). LncRNA Meg3 can aggravate UUO-induced rat renal fibrosis by activating the hedgehog pathway.

Refinement of the acute inhalation limit test for inert, nano-sized dusts by an in silico dosimetry-based evaluation: case study for the dissolution of a regulatory dilemma.

This case study aims to describe the dilemma faced when exposing rats to very high concentrations of fine, pulverulent materials for acute inhalation studies and to address the regulatory question of whether the effects seen here are relevant to humans and the subject of classification according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS). Many powders match the definition of nanomaterials in the EU; therefore, information on acute inhalation testing of powders up to the GHS cutoff of 5mg/L is required. However, testing rats at such a high aerosol concentration can cause physical obstruction of the airways and even mortality by suffocation. Therefore, to evaluate whether the physical effects on airway obstruction in rats exposed to 5mg/L for 4hours and alternative exposures to 1 and 2mg/L are relevant for humans, an in silico evaluation of aerosol deposition was conducted using the multiple-path particle dosimetry (MPPD) model. For this evaluation, actual exposure conditions for an organic, nano-sized pigment which produced 100% lethality in rats at 5mg/L, but not at 1mg/L, were used to assess the potential for airway obstruction in rats and accordingly in humans. As an indicator of the potential for airway obstruction, the ratio of the diameter of the deposited, aggregated aerosol to airway diameter was calculated for each exposure condition. For rats exposed to 5mg/L for 4h, approximately 75% of tracheobronchial and 22% of pulmonary/alveolar airways were considered vulnerable to significant or complete obstruction (ratios >0.5). In humans, an equivalent exposure resulted in just over 96% of human tracheobronchial airways that received deposited mass to airway diameter ratios between 0.3 and 0.4 (nasal) or 0.4 and 0.5 (oral), with no airways with ratios >0.5. For the pulmonary/alveolar region, ∼88% of the airways following nasal or oral breathing were predicted to have deposited aerosol diameter to airway diameter ratios <0.1, with no airways with ratios >0.5. Thus, the in silico results obtained for rats are in line with the pathological findings of the animal test. The predicted results in humans, however, affirm the hypothesis of a rat-specific high dose effect which does not justify a classification according to GHS.

Hypoxia caused by unilateral nasal obstruction decreases mandibular density in rats through inhibition of Cyp1a1 expression.

Oral breathing has an important impact on morphology and bone mineral density (BMD) in a mandible. This study aimed to investigate the hub genes and mechanism regulating the mandibular BMD decrease induced by nasal obstruction. A unilateral nasal obstruction model was established in 1-week-old Wistar rats by electrocautery obstruction. BMD of the mandible was determined by micro-computed tomography. Transcriptome analysis was performed to identify differentially expressed genes (DEGs). Hub genes were identified by building protein-protein interaction network and verified by western blot. A hypoxic cell model was established in bone marrow mesenchymal stem cells (BMSCs) by using CoCl2. The expression of hypoxia-inducible factor-1α (HIF-1α), NF-kB ligand-receptor activator (RANKL), osteoprotegerin (OPG), and Cyp1a1 was detected by western blot. The mandibular BMD of rats in the unilateral nasal obstruction group was significantly decreased. A total of 38 DEGs were identified in nasal obstruction rats compared with normal rats. A ratio of RANKL/OPG in the mandible was elevated by nasal obstruction, while the Cyp1a1 was decreased. In vitro, the HIF-1α expression and RANKL/OPG ratio were upregulated by hypoxia while the Cyp1a1 expression was decreased. Pretreatment with Cyp1a1 activator, FICZ, could increase the expression of Cyp1a1 while attenuating the activation of HIF-1α and RANKL. Respiratory changes caused by nasal obstruction contribute to the decrease in Cyp1a1 expression in the mandible of juvenile rats, which is associated with disturbances in bone homeostasis controlled by the RANKL/OPG ratio.

Retracted: PKC-delta and PKD activate MAPK signal pathway in mechano-transcription of colonic smooth muscle cells.

Retraction: [PKC-delta and PKD activate MAPK signal pathway in mechano-transcription of colonic smooth muscle cells, Z. Yang, K. He, T. Wang, et al. Neurogastroenterology & Motility 2023; e14623 (https://onlinelibrary.wiley.com/doi/full/10.1111/nmo.14623)]. The above article, published online on June 6, 2023 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the Journal Editor in Chief, Maura Corsetti, and John Wiley & Sons Ltd. The retraction has been agreed due to unat[1]tributed overlap between this article and the abstract published in Gastroenterology: Li F, Sarna SK and Shi XP. Roles of PKCs and PKD in Mechanotranscription in Colonic Smooth Muscle Cells: Inhibition of Mechanotranscription as a Potential Treatment for Motility Dysfunction in Obstructive Disorders. In: 2012 Digestive Disease Week Abstract Supplement; May 19-22, San Diego, CA. Abstract 120 (https://www.gastrojournal.org/article/S0016-5085(12)60115-2/pdf).

Analysis of gut microbiota in rats with bile duct obstruction after biliary drainage

The abundance of specific gut microorganisms is strongly associated with the concentrations of microbially modified bile acids. This study aimed to investigate the composition of intestinal microbiota in rats subjected to bile duct ligation or biliary drainage. Extrahepatic bile duct ligation was conducted to induce bile duct obstruction in rats. The bile was drained via a percutaneous biliary drainage catheter to cause bile deficiency. The total DNA extracted from fecal samples was sequenced with 16S DNA sequencing. Taxonomic classifications were conducted using the Mothur algorithm and SILVA138 database and were presented along with the abundance presented using a heatmap. The inter- and intra-group differences in the intestinal microbiome composition were analyzed by ANOSIM test. The biomarker microorganisms were screened using the Linear discriminant analysis Effect size method. The possible functional pathways were predicted using the Tax4Fun package. A total of 3277 operational taxonomic units (OTUs) were examined, with 2410 in the Kongbai group, 2236 in the Gengzu group, and 1763 in the Yinliu group. The composition of microorganisms at the levels of phylum, class, order, family, and genus was altered in rats with bile duct obstruction. This composition was then restored by biliary drainage. The top 10 predominant microorganisms were identified that led to the inter-group differences. Functional annotation revealed that the potential functions of the microorganisms with significant differences were enriched in metabolism, cellular processes, and genetic and environmental information processing. The intestinal microbial community was significantly changed in rats with bile duct obstruction. The changes in the abundance of intestinal microbiota Prevotellaceae and Enterobacteriaceae were statistically significant after biliary drainage treatment.

On-skin biosensors for noninvasive monitoring of postoperative free flaps and replanted digits

Severe soft tissue defects and amputated digits are clinically common injuries. Primary treatments include surgical free flap transfer and digit replantation, but these can fail because of vascular compromise. Postoperative monitoring is therefore crucial for timely detection of vessel obstruction and survival of replanted digits and free flaps. However, current postoperative clinical monitoring methods are labor intensive and highly dependent on the experience of nurses and surgeons. Here, we developed on-skin biosensors for noninvasive and wireless postoperative monitoring based on pulse oximetry. The on-skin biosensor was made of polydimethylsiloxane with gradient cross-linking to create a self-adhesive and mechanically robust substrate that interfaces with skin. The substrate was shown to exhibit appropriate adhesion on one side for both high-fidelity measurements of the sensor and low risk of peeling injury to delicate tissues. The other side demonstrated mechanical integrity to facilitate flexible hybrid integration of the sensor. Validation studies using a model of vascular obstruction in rats demonstrated the effectiveness of the sensor in vivo. Clinical studies indicated that the on-skin biosensor was accurate and more responsive than current clinical monitoring methods in identifying microvascular conditions. Comparisons with existing monitoring techniques, including laser Doppler flowmetry and micro-lightguide spectrophotometry, further verified the sensor's accuracy and ability to identify both arterial and venous insufficiency. These findings suggest that this on-skin biosensor may improve postoperative outcomes in free flap and replanted digit surgeries by providing sensitive and unbiased data directly from the surgical site that can be remotely monitored.

The Effect of Celery Ethanol Extract on Proteinuria in Unilateral Ureter Obstruction Rat Model

Chronic kidney disease (CKD) is a condition of decreased kidney function that occurs for more than three months. Proteinuria is one of the markers of impaired kidney function, especially in the renal filtration process. Unilateral ureter obstruction causes impaired kidney function, including the filtration process. Celery (Apium graveolens L.) contains phenolic compounds that can prevent the decrease of kidney function. This study aims to determine the effect of celery ethanol extract on proteinuria in the UUO rat model. This study was an experimental study with a post-test only with control group design. A total of 25 rats were assigned to 5 groups. Group 1: sham control, 2: negative control (UUO), 3: UUO with 125 mg/kgBW celery ethanol extract, 4: UUO with 250 mg/kgBW celery ethanol extract, and 5: UUO with 500 mg/kgBW celery ethanol extract. The treatment of celery ethanol extract was given for 14 days. Urine samples were taken on the 15th day for examination of proteinuria. The results were analyzed by the Oneway ANOVA test and showed a significant difference between the control group and the treatment groups (p&lt;0.05). A dose of 250mg/kgBW is the most effective dose of celery ethanol extract in this study.

Role of Cannabinoid Type 2 Receptor Activation in Renal Fibrosis Induced by Unilateral Ureteric Obstruction in Rats.

Chronic kidney disease (CKD) ends mostly with renal fibrosis. The effect of CB2 receptor on renal fibrosis has been unclear. The aim of this study was to investigate the effect of CB2 receptor on renal fibrosis and the mechanisms behind it. 50 adult male Sprague-Dawley rats were divided into 5 groups; normal, sham; rats had their ureters only manipulated, UUO; rats had their left ureters ligated, and JWH post; rats had their left ureters ligated and they received JWH 133 for 14 days, JWH pre+post; rats received JWH 133 for 14 days before and after UUO procedure. Serum creatinine and BUN were assessed together with tissue MDA, GSH, and catalase. Histopathological evaluation of the renal tissue by H&E and Masson's trichrome was done. Immunohistochemical staining for TGF-β1, AQP1, Caspase-3, LC3B and p62 was performed. AQP1 and CB2 receptors genes expression was detected by quantitative RT-PCR. UUO had caused severe damage in the renal tissue with reduction of the renal function parameter accompanied by increase in the collagen deposition with increase TGF-β1 and decrease AQP1 expression. The improvement of these parameters with JWH-133 suggests an anti-fibrotic role of CB2 receptor activation through reduction of oxidative stress, apoptosis, and autophagy.

MP03-19 ROLE OF MICROFIBRILLAR-ASSOCIATED PROTEIN 4 IN PARTIAL BLADDER OUTFLOW OBSTRUCTION-RELATED BLADDER FIBROSIS

You have accessJournal of UrologyCME1 Apr 2023MP03-19 ROLE OF MICROFIBRILLAR-ASSOCIATED PROTEIN 4 IN PARTIAL BLADDER OUTFLOW OBSTRUCTION-RELATED BLADDER FIBROSIS Reine Kanaan, Anders Schlosser, Grith Lykke Sorensen, and Peter Zvara Reine KanaanReine Kanaan More articles by this author , Anders SchlosserAnders Schlosser More articles by this author , Grith Lykke SorensenGrith Lykke Sorensen More articles by this author , and Peter ZvaraPeter Zvara More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003214.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Partial bladder outflow obstruction (pBOO) causes remodeling of the bladder wall, with smooth muscle hypertrophy and an excessive deposition of extracellular matrix (ECM) proteins, leading to bladder fibrosis. Our understanding of the pathophysiology of this process is limited and no effective treatment to prevent or reverse bladder fibrosis exists. Microfibrillar-associated protein 4 (MFAP4) is an ECM glycoprotein, localized to elastic fiber-rich regions. It binds ECM components including elastin and collagen and contributes to the process of elastogenesis in healthy tissues. Emerging data suggest the involvement of MFAP4 in the pathogenesis of disease-induced tissue remodeling, including fibrosis. To determine its value as a potential therapeutic target, we compared MFAP4 expression in sham-operated bladders to bladders 6 weeks following pBOO. MFAP4 levels were then correlated with bladder function. METHODS: Partial BOO, was induced in 9 male Sprague Dawley rats, 5 underwent sham surgery. Six weeks following surgery, rats were placed in a metabolic cage overnight to record 12-hour micturition frequency and volume per void. Gene expression levels of MFAP4, alpha-smooth muscle actin (α-SMA) and collagen I were quantified in the bladder tissue using real-time PCR. RESULTS: The bladder/body ratio was significantly higher in the pBOO group (0.07±0.04) when compared to the SHAM group (0.024±0.003). Obstructed rats with increased MFAP4 expression demonstrated an increase in α-SMA expression. No significant increase in collagen I levels was recorded in the pBOO group. Animals with bladder overactivity as determined by frequent low volume micturitions (≥4 micturitions with <0.1 mL per void/12 hours) had higher MFAP4 expression than animals in the SHAM group, which exhibited normal micturition pattern. CONCLUSIONS: These initial observations show that pBOO lasting 6 weeks results in detrusor hypertrophy. Although bladder wall fibrosis did not develop within the 6-week timeframe, our data suggest that bladder remodeling following pBOO is associated with increased MFAP4 levels and that MFAP4 might be involved in the pathogenesis of pBOO-induced bladder dysfunction. Experiments addressing processes extending beyond 6 weeks post-pBOO and possible involvement of MFAP4 in their pathophysiology are ongoing. Source of Funding: Odense University hospital © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e31 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Reine Kanaan More articles by this author Anders Schlosser More articles by this author Grith Lykke Sorensen More articles by this author Peter Zvara More articles by this author Expand All Advertisement PDF downloadLoading ...

Huoxue Jiedu Huayu recipe alleviates contralateral renal fibrosis in unilateral ureteral obstruction rats by inhibiting the transformation of macrophages to myofibroblast.

Huoxue Jiedu Huayu recipe alleviates contralateral renal fibrosis in unilateral ureteral obstruction rats by inhibiting the transformation of macrophages to myofibroblast.

PS-B03-9: EPLERENONE PREVENTS CARDIAC FIBROSIS BY INHIBITING ANGIOGENESIS IN UNILATERAL URINARY OBSTRUCTION RATS

Objective: Cardiovascular disease constitutes the leading cause of mortality in patients with chronic kidney disease (CKD), which is termed cardiorenal syndrome type 4 (CRS-4). The aim of our experiments was to clarify the relationship between angiogenesis and endothelial-mesenchymal transition (End-MT) and the the development of pathological cardiac remodeling and fibrosis in unilateral urinary obstruction (UUO) rats. Also, our study was to confirm eplerenone prevents cardiac fibrosis by inhibiting angiogenesis in unilateral urinary obstruction rats. Design and method: We used a 180-day rat model of unilateral ureteral obstruction (UUO) to replicate the CRS model. Using eplerenone, a blocker of mineralocorticoid receptor (MR), to test the effect of aldosterone in cardiac fibrosis induced by UUO. HE staining was performed to observe the pathology of myocardial tissue. The degree of myo-cardial tissue fibrosis was observed by Masson and Sirius red staining. Immunohistochemical staining was applied to detect the expression of CD34 and CD105 in myocardial tissue, and immunofluorescent staining was performed to examine the expression of CD34, COLI/COLIII and alpha-SMA. The expression of signal pathway-related protein VEGFA, VEGFR2, nuclear factor kappa-B and IL-1 beta were tested by western blot. RT-PCR was used to detect the mRNA levels of SGK-1, nuclear factor kappa-B and IL-1beta. Results: The results shows that the development of pathological cardiac remodeling and cardiac dysfunction in UUO rats. Moreover, there was more angiogenesis and endothelial-mesenchymal transition (End-MT) in the UUO group, and these effects were inhibited by eplerenone. Conclusions: The results indicated that this cardiac fibrosis was associated with angiogenesis and endothelial-mesenchymal transition (End-MT) related to aldosterone and mineralocorticoid receptor (MR) activation. Moreover, in association with the MR/IL-1beta/VEGFA signaling pathway, early treatment with the MR antagonist eplerenone in rats with UUO-induced CKD may significantly attenuate MR activation and cardiac fibrosis.