缬沙坦和氟伐他汀对糖尿病大鼠肾脏的保护作用及对ICAM-1表达的影响

Protective effects of valsartan and fluvastatin on the kidneys of diabetic rats and expression of ICAM-1

目的从影响细胞间黏附分子-1(ICAM-1)表达的角度,探讨血管紧张素Ⅱ受体拮抗剂缬沙坦和羟甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂氟伐他汀对糖尿病大鼠肾脏病变的保护作用及其可能机制。方法通过链脲佐菌素诱导建立糖尿病大鼠模型并进行分组,检测肾重、肾脏肥大指数、血糖、血脂、血肌酐、尿素氮、24 h尿蛋白定量,应用免疫组织化学法和逆转录聚合酶链反应(RT-PCR)分别从蛋白及mRNA水平检测肾组织ICAM-1的表达,光镜及电镜下观察肾组织病理学改变,并应用计算机图像分析系统进行定量分析。结果单药及两药联用组肾脏肥大指数、24 h尿蛋白定量、血脂、血肌酐、尿素氮、肾组织ICAM-1表达均与糖尿病模型组有明显差异(P<0.05或P<0.01)。各治疗组肾脏病理改变有不同程度的减轻,以两药合用组减轻最明显。结论ICAM-1参与了糖尿病肾病的发生和发展,氟伐他汀和缬沙坦均可降低糖尿病大鼠肾脏ICAM-1的表达,且两药联用对糖尿病大鼠肾脏具有协同保护作用。

Objective To investigate the protective effects of angiotension Ⅱ receptor antagonist valsartan and hydroxymethyl-glutaryl coenzyme A （HMG-CoA） reductase inhibitor fluvastatin on the kidneys of diabetic rats,and study their possible mechanisms related to intercelluar adhesion molecule-1 （ICAM-1）expression. Methods Rats were divided into the normal control rats （group NC ）, streptozotocin-induced diabetic rats （group DM）, diabetic rats treated with valsartan （group DV）, diabetic rats treated with fluvastatin （group DF） and diabetic rats treated with valsartan and fluvastatin（ group DVF）. Intrarenal ICAM-1 content and mRNA expression were measured by immunohistochemical technique and reverse transcriptas-polymerase chain reaction （RT-PCR）technique respectively. Pathological changes of renal tissue were observed through light microscopy and electron microscopy. Results There were significant differences in kidney hypertropathy index,24-hour urinary protein, lipid, blood urea nitrogen（ BUN）, serum creatinine （Scr）and expression of ICAM-1 between treated diabetic rats and untreated diabetic rats（P 〈0.05 or P 〈0.01 ）. Pathological changes on kidney were much lighter in treated group than that in group DM. Conclusion Glomerular ICAM-1 expression may increase in diabetic nephropathy,which contributing to the occurance and development of diabetic nephropathy. Fluvastatin and valsartan both seem to have renal protective effects on kidney of diabetic rats. Combination of them seems to confer further benefits to prevent renal damage of diabetic rats.