【摘要】 目的 观察链脲佐菌素(STZ)诱导的糖尿病Wistar大鼠在糖尿病对照、糖尿病分别用氯沙坦、辛伐他汀以及用辛伐他汀和氯沙坦联合治疗的4种条件下肾脏NF-κB、PKCα 及 PDGF-B表达的情况，以阐明NF-κB、PKCα 及 PDGF-B 在糖尿病大鼠肾脏中的变化和药物作用的可能机制。方法 用放射免疫法测尿白蛋白并计算12h尿蛋白排泄率(UAER)，同时测FBG、血胆固醇、血甘油三酯、血肌酐。肾组织切片HE染色镜下观察糖尿病肾脏常规病理变化。用SABC免疫组化方法检测各组肾小球、肾小管NF-κB、PKCα 及 PDGF-B三种蛋白的表达情况。用图像采集分析软件对免疫组化染色情况进行定量分析。结果 (1)糖尿病8周末，NF-κB、PDGF-B及PKCα在肾组织的表达显著增高(与正常对照比P<0.05)。HE染色未见糖尿病肾病特有的结节型或弥漫型肾小球硬化表现，但糖尿病对照组可见明显的肾小管上皮细胞的空泡样变性，而正常或药物治疗组未见相应改变。UAER高达90μg/min以上，明显高于正常对照组(P<0.0001)。(2)辛伐他汀和氯沙坦各自单独治疗均可使以上指标的表达显著抑制(与糖尿病对照比P<0.05)，而且辛伐他汀的治疗作用独立于其降脂作用，但均达不到正常对照水平,两药联合使用可使表达水平进一步下降和改善。结论 NF-κB、PDGF-B及PKCα的表达对糖尿病肾病起着重要的作用。氯沙坦的肾脏保护作用不同于脂类代谢的作用、氯沙坦和辛伐他汀的联合应用可以更好地保护肾脏，但它们真正的作用机制有待进一步的研究。

    关键词 氯沙坦 辛伐他汀 糖尿病肾病 蛋白激酶Cα 血小板衍化生长因子-B链

    Effects of losartan and simvastatin on the expressions of NF-κB，PDGF-B and PKCα in renal tissue of STZ-induced diabetic rats

    Shao Jinkang,Liang Jianfang，Qin Jie

    Department of Endocrinology, Shanxi Province People’s Hospital, Taiyuan 030012.

    【Abstract】 Objective The excessive expressions of TGF-β,VEGF in renal tissue of diabetic rats has been reported recent years, and the changes could be inhibited with losartan and fluvastatin. But exact action mechanism is not very clear. To research the effects of NF-κB、PKCα and PDGF-B on the progression of diabetic nephropathy and the renoprotective mechanism of losartan and Simvastatin on Streptozotocin-induced diabetic Wistar rats, the study item was designed.Methods The 60 Wistar rats were randomly divided into following 5 groups: normal control (n=8,C group), diabetes control (n=13, D group), diabetic rats treated with losartan[20mg/(kg·d), by gavage, n=13,D1 group], diabetic rats treated with simvastatin[2mg/(kg·d), by gavage, n=13,D2 group] and diabetic rats treated with losartan and simvastatin[20mg/(kg·d) and 2mg/(kg·d), by gavage, n=13,D3 group].All rats of diabetic groups were not treated with insulin or other anti-diabetes drugs. At the end of the 8th week of study, protein expressions of NF-κB、PKCα and PDGF-B in kidney were measured by immunohistochemistry, and 12-hour urine albuminuria excretion rate(UAER),plasma cholesterol,plasma triglyceride and plasma creatinine were determined with biochemistry .Results After 8 weeks ,the expressions of NF-κB,PKCα and PDGF-B in diabetic renal tissue were significantly increased(P<0.05). The means of UAER in diabetic control group was also significant different from other groups and was more than 90μg/min . The immunohistochemistry staining of NF-κB,PKCα and PDGF-B in kidney proximal tuble cytoplasma was more than that in glomeruler. Epithelial cells of kidney tuble were found vacuolar degeneration with hematoxylin-eosin staining(HE staining) by light microscopy . Both losartan and simvastatin could significantly inhibit the expressions of NF-κB,PKCα and PDGF-B in diabetic renal tissue(P<0.05),but could not make it recovery. Combined treatment of losartan and simvastatin could inhibit the expressions of NF-κB,PKCα and PDGF-B further. In general, effects between losartan and simvastatin were not significant difference.Conclusion NF-κB,PKCα and PDGF-B play an important action on the progression of diabetic nephropathy. It shouldn’t be ignored that they might injure kidney tuble . Both losartan and simvastatin have significant effect on diabetic nephropathy. The renoprotective effect of losartan is independent upon it’s effect of regulating lipoid metabolism. Combined treatment of losartan and simvastatin could further protect kidney from diabetic injury. But their exact mechanism remains to be further studied. ......