雷米普利对糖尿病大鼠肾脏保护作用的影响及其机制研究

摘要

Objective To observe the changes of renal pathology and the protein expression of Megsin, PAI-1 and IGF-1 with the ramipril intervention, in order to study the protective mechanisms of ramipril. Methods 48 healthy male SD rats were randomly divided into three groups:normal control group (Group A, n=12);diabetic rat models were established with peritoneal injection of streptozotocin ( blood glucose≥16. 7 mmol/L) and the successful 24 models were divided into dia-betic group (Group B, n=12) and ramipril intervention group [1 mg/(kg·d), Group C, n=12]. 12 weeks later, the blood, urine and kidney samples were collected for further analysis; the weight, 24 h urine, blood glucose and kidney/body weight ratio, the amount of 24 h urinary protein and serum creatinine clearance rate were compared. The histopathological changes of renal tissues were also observed. And the protein expression of Megsin, PAI-1 and IGF-1 were respectively meas-ured by immunohistochemistry and western blot. Results Compared with that of Group A, the body weight loss was greater, the 24 h urine, blood glucose and kidney/body weight ratio and serum creatinine clearance rate increased more in Group B and C with statistical significance (P<0. 05). The 24 h urine and serum creatinine clearance rate were obviously decreased in Group C (P<0. 05). There was no significant renal pathological change in Group A, while there was in Group B. Mean-while, in Group B, the mesangial area became wider, PAS stain positive materials and the expression of Megsin, PAI-1 and IGF-1 increased more significantly than that in Group A (P<0. 05). Conclusion Ramipril can alleviate pathological changes of diabetic rats, and lower the expression of Megsin, PAI-1, IGF-1 in renal tissues, and with a protective effect.%目的：观察雷米普利对糖尿病大鼠肾脏病理学变化及肾组织中Megsin、血浆纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor-1, PAI-1)和胰岛素样生长因子-1(insulin-like growth factor-1, IGF-1)表达的影响,探讨其肾保护机制。方法取健康雄性SD大鼠48只,其中12只作为正常对照组( A组),余均一次性腹腔注射链脲佐菌素建立糖尿病大鼠模型(血糖≥16．7 mmol/L),将建模成功的24只随机均分为雷米普利干预组[C 组,雷米普利1 mg/( kg·d)灌胃]和糖尿病组( B组,等量注射用水灌胃)。12周后,收集各组大鼠血、尿及肾组织标本,比较各组体重、24 h 尿量、血糖、肾重与体重比、尿蛋白定量和肌酐清除率,观察各组肾组织病理学变化,并采用免疫组织化学染色及Western blot法测定各组大鼠肾组织Megsin、PAI-1及IGF-1蛋白的表达。结果与A组比较,B、C组体重减轻,24 h尿量、血糖明显增加,肾重与体重比、24 h尿蛋白定量、肌酐清除率明显升高,差异均有统计学意义( P<0．05)；C组24 h尿蛋白定量、肌酐清除率较B组显著降低( P<0．05)。 A组肾脏无明显病理改变；B组肾脏病理改变明显,系膜区增宽、PAS染色阳性物质增多,肾组织Megsin、PAI-1、IGF-1蛋白表达明显高于A组( P<0．05)；C组肾脏病理变化较B组轻,肾组织Megsin、PAI-1及IGF-1蛋白表达较B组下降但仍高于A组,差异均有统计学意义(P<0．05)。结论雷米普利能减轻糖尿病大鼠肾脏病理学变化,并下调Megsin、PAI-1、IGF-1在肾小球中的表达,具有肾保护作用。