ABSTRACT
BACKGROUND: In China, mesangial proliferative glomerulonephritis (MsPGN) is one of the most common kidney diseases. In this study, we treated a rat model of chronic anti-Thy-1 MsPGN with Shenhua Tablet and evaluated whether the tablet was able to protect the kidney function. Thirty-six Wistar rats were randomly divided into six groups: (1) Sham surgery (Sham); (2) anti-Thy-1 nephritis model (Thy-1); (3) anti-Thy-1 nephritis model + irbesartan-treated (Irb); (4) anti-Thy-1 nephritis model + low-dose of Shenhua Tablet (SHL); (5) anti-Thy-1 nephritis model + medium-dose of Shenhua Tablet (SHM); (6) anti-Thy-1 nephritis model + high-dose of Shenhua Tablet (SHH). RESULTS: Thirteen weeks after drug treatment, urinary proteins were quantified and renal pathological changes were thoroughly examined at the time point of 24 h. Meanwhile, the expression levels of p-Erk1/2, cyclin D1 and p21 at the renal cortex were also tested. The levels of urinary proteins and total cholesterol in the blood were significantly reduced in rats treated with any drug tested in this study. The level of triglyceride was significantly reduced in all three Shenhua Tablet-treated groups. Renal pathomorphological scores were significantly improved in groups of Irb, SHM and SHH. Mesangial cell proliferation was significantly inhibited in any drug-treated group. p-Erk1/2 and cyclin D1 were downregulated whereas p21 was upregulated in the renal cortex. CONCLUSIONS: Our study indicated that Shenhua Tablet is able to inhibit the abnormal proliferation of mesangial cells and to prevent kidney damage, which is likely associated with downregulation of p-Erk1/2 and reduced activity of its downstream target-cyclin D1.
Subject(s)
Animals , Male , Drugs, Chinese Herbal/pharmacology , Glomerulonephritis, Membranoproliferative/drug therapy , Cell Proliferation/drug effects , Mesangial Cells/drug effects , Isoantibodies , Time Factors , Serum Albumin/analysis , Drugs, Chinese Herbal/therapeutic use , Glomerulonephritis, Membranoproliferative/pathology , Chronic Disease , Reproducibility of Results , Rats, Wistar , Mitogen-Activated Protein Kinase 1/analysis , Cyclin D1/analysis , Computers, Handheld , p21-Activated Kinases/analysisABSTRACT
Objective: To evaluate the effect of mesenchymal stem cells (MSCs) in rats with anti-Thy1,1 nephritis. Methods: Female albino rats were divided into three groups, control group, anti-Thy1,1 group and treatment with i.v. MSCs group. MSCs were derived from bone marrow of male albino rats, Y-chromosome gene was detected by polymerase chain reaction in the kidney. Serum urea and creatinine were estimated for all groups. Kidney of all studied groups was examined histologically and histochemically (total carbohydrates and total proteins). DNA fragmentation and expression of α-SMA were detected. Results:Kidney of animals injected with anti-Thy1,1 showed inflammatory leucocytic infiltration, hypertrophied glomeruli, tubular necrosis and congestion in the renal blood vessels. The kidney tissue also showed reduction of carbohydrates and total proteins together with increase in apoptosis and in expression ofα-SMA. Moreover, the levels of urea and creatinine were elevated. Treating animals with MSCs revealed that kidney tissue displayed an improvement in the histological and histochemical changes. Apoptosis and α-SMA expression were decreased, and the levels of urea and creatinine decreased. Conclusions:The obtained results demonstrated the potential of MSCs to ameliorate the structure and function of the kidney in rats with anti-Thy1,1 nephritis possibly through the release of paracrine growth factor(s).
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect of mesenchymal stem cells (MSCs) in rats with anti-Thy1,1 nephritis.</p><p><b>METHODS</b>Female albino rats were divided into three groups, control group, anti-Thy1,1 group and treatment with i.v. MSCs group. MSCs were derived from bone marrow of male albino rats, Y-chromosome gene was detected by polymerase chain reaction in the kidney. Serum urea and creatinine were estimated for all groups. Kidney of all studied groups was examined histologically and histochemically (total carbohydrates and total proteins). DNA fragmentation and expression of α-SMA were detected.</p><p><b>RESULTS</b>Kidney of animals injected with anti-Thy1,1 showed inflammatory leucocytic infiltration, hypertrophied glomeruli, tubular necrosis and congestion in the renal blood vessels. The kidney tissue also showed reduction of carbohydrates and total proteins together with increase in apoptosis and in expression of α-SMA. Moreover, the levels of urea and creatinine were elevated. Treating animals with MSCs revealed that kidney tissue displayed an improvement in the histological and histochemical changes. Apoptosis and α-SMA expression were decreased, and the levels of urea and creatinine decreased.</p><p><b>CONCLUSIONS</b>The obtained results demonstrated the potential of MSCs to ameliorate the structure and function of the kidney in rats with anti-Thy1,1 nephritis possibly through the release of paracrine growth factor(s).</p>
Subject(s)
Animals , Female , Male , Rats , Isoantibodies , Toxicity , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Metabolism , Nephritis , General SurgeryABSTRACT
@#Objective To determine the renal effects of chronic exercise training and enalapril in uninephrectomized anti-Thy-1 nephritis Wistar rats (Thy-1-Crf). Methods 5-week-old Wistar rats were subjected to uninephrectomy. Anti-Thy-1 nephritis was induced by injecting 200 μg/kg OX-7 intravenously once a week for four times. They were divided into 3 groups: non exercise; moderate exercise with treadmill running(20 m/min, 0 grade-incline for 60 min); moderate exercise with an angiotensin converting enzyme(ACE) inhibitors, enalapril (2 mg/kg/day i.p.) for 8 weeks.Results Exercise did not suppress the increase in proteinuria in Thy-1-Crf. However, enalapril significantly decreased systolic blood pressure(SBP), urinary protein excretion(UpE), and index of glomerular sclerosis (IGS) in Thy-1-Crf. Conclusion The renal protective effects of moderate exercise in models of renal failure differ depending on the etiology of renal failure. It also suggests that enalapril can widen the acceptable range of exercise intensity in Thy-1-Crf.
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Purpose To investigate the significance of u-PA and PAI-1 expression on the glomeruli,and the effect of heparin on their expressions in rat anti-thy1 glomerulonephritis. Methods We analyzed the cell proliferation and the expression of u-PA/PAI-1 on the glomeruli by immunohistochemistry and quantitative analysis of immunostaining. Results The cell proliferation of the glomeruli decreased significantly at 7 th,14 th,21 st day after heparin treatment in comparison to the glomerulonephritic group(P<0.05 or 0.01).The expression of u-PA and PAI-1 on the glomeruli in glomerulonephritic and heparin-treated groups was higher than that in the control group.At 3 rd,7 th,14 th,21 st day,the glomerular hypercellularity in the glomerulonephritic group was closely related to the increased expression of u-PA and PAI-1(P<0.05 or 0.01).At 3 rd,7 th day,the decreased cell proliferation of the glomeruli in heparin-treated group had close relationship with the decreased expression of PAI-1(P<0.05). Conclusions In rat anti-thy 1 glomerulonephritis model,the expression of u-PA and PAI-1 increased with glomerular hypercellularity;heparin treatment can decrease the extent of glomerular hypercellularity in rat anti-thy 1 glomerulonephritis.The treatment function of heparin might be related with the inhibitory effect of PAI-1 expression on the glomeruli.