title: Renoprotective effect of benazepril on diabetic nephropathy mediated by P42/44MAPK.
abstract: The effects of benazepril on P42/44MAPK, angiotensin II expression in renal tissue and renal pathological change of the experimental diabetic rats were assessed and the possible mechanism of benazepril's renoprotective effect was explored. Adult male Wistar rats, 11-12 weeks age, weighing initially 160 to 200 g were randomly allocated into 2 groups: control group (A, n = 6) and experimental group (n = 12). Diabetic rats in experimental group were rendered diabetic by intraperitoneal injection of Streptozotocin (60 mg/kg body weight), and randomly subdivided into B group (diabetic control) and C group (diabetic rats treated with benazepril, 6 mg/kg every day). Studies were performed 8 weeks after induction of diabetes. Twenty-four h urine of every rat was collected to detect urine creatinine. Serum glucose concentration and serum creatinine were determined by collecting blood samples from the inferior vena cava. Body and kidney weight were recorded. Creatinine clearance (Ccr) and ratio of kidney weight to body weight were calculated. Plasma and renal tissue angiotensin II concentration was assayed by radioimmunoassay (RIA). The phospo-p44/42MAPK protein expression was detected by Western-blot. The results showed that benazepril had no significant effect on the blood glucose level in diabetic rats in two experimental groups. Ccr and ratio of kidney weight to body weight were increased in group B (P < 0.01) as compared with normal rats at the end of the 8th week. At the end of the 8th week, Ccr in group C was lower than that in group B (P < 0.01). The ratio of kidney weight to body weight in group C was lower than that in group B at the 8th week. There were glomeruli hypertrophy and slight or moderate mesangium proliferation in diabetic rats, while there was fragmentally proliferative mesangium in group C at the end of the 8th week. Renal tissue angiotensin II concentration was significantly increased in group B, while benazepril could significantly decrease the concentration of angiotensin II in renal tissue. The expression of the phospo-p44/42MAPK protein in group B was increased as compared with group A, while it was decreased in group C as compared with group B. P42/ 44MAPK pathway participated in the pathogenesis of diabetic nephropathy. Benazepril can eliminate high filtration of glomeruli, decrease proteinuria, and eliminate renal hypertrophy as well as renal destruction. Renoprotective effect of benazepril in diabetic rats may be partly related to the inhibition of angiotensin II -P42/44MAPK pathway.
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yongman
authors.initials: Y
authors.lastname: Lv
authors.forename: Junwu
authors.initials: J
authors.lastname: Dong
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Niu
authors.forename: Xiaocheng
authors.initials: X
authors.lastname: Liu
mesh_terms: D000804:Angiotensin II / Q000096:biosynthesis / Q000235:genetics; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003928:Diabetic Nephropathies / Q000378:metabolism*; D007677:Kidney Function Tests; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis* / Q000235:genetics; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis* / Q000235:genetics; D020011:Protective Agents / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D020011:Protective Agents; D000804:Angiotensin II; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C044946:benazepril