Lv Yongman, Dong Junwu, Niu Xiaochun, Liu Xiaocheng
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
J Huazhong Univ Sci Technolog Med Sci. 2005;25(1):32-5. doi: 10.1007/BF02831380.
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.
评估贝那普利对实验性糖尿病大鼠肾组织中P42/44MAPK、血管紧张素II表达及肾脏病理变化的影响，并探讨贝那普利肾脏保护作用的可能机制。选取11 - 12周龄、初始体重160至200 g的成年雄性Wistar大鼠，随机分为2组：对照组（A组，n = 6）和实验组（n = 12）。实验组糖尿病大鼠通过腹腔注射链脲佐菌素（60 mg/kg体重）诱导糖尿病形成，再随机分为B组（糖尿病对照组）和C组（糖尿病大鼠用贝那普利治疗组，每天6 mg/kg）。糖尿病诱导8周后进行研究。收集每只大鼠24小时尿液检测尿肌酐。通过从下腔静脉采集血样测定血清葡萄糖浓度和血清肌酐。记录体重和肾脏重量。计算肌酐清除率（Ccr）和肾脏重量与体重之比。采用放射免疫分析法（RIA）测定血浆和肾组织血管紧张素II浓度。通过蛋白质免疫印迹法检测磷酸化p44/42MAPK蛋白表达。结果显示，贝那普利对两个实验组糖尿病大鼠的血糖水平无显著影响。第8周结束时，B组的Ccr和肾脏重量与体重之比与正常大鼠相比升高（P < 0.01）。第8周结束时，C组的Ccr低于B组（P < 0.01）。第8周时，C组的肾脏重量与体重之比低于B组。糖尿病大鼠存在肾小球肥大和轻度或中度系膜增生，而第8周结束时C组存在局灶性系膜增生。B组肾组织血管紧张素II浓度显著升高，而贝那普利可显著降低肾组织血管紧张素II浓度。与A组相比，B组磷酸化p44/42MAPK蛋白表达增加，而与B组相比，C组该蛋白表达降低。P42/44MAPK途径参与糖尿病肾病的发病机制。贝那普利可消除肾小球高滤过，减少蛋白尿，消除肾脏肥大及肾脏破坏。贝那普利对糖尿病大鼠的肾脏保护作用可能部分与抑制血管紧张素II - P42/44MAPK途径有关。
