P-选择素在1型糖尿病肾病大鼠发病中的作用

目的:探讨P-选择素在糖尿病肾病发病中的作用和低分子肝素法安明对肾脏保护作用及机制。方法:用链脲佐菌素(60mg/kg体重)构建1型糖尿病大鼠模型后随机分为4组,正常对照(N)组、糖尿病(DN)组、法安明大剂量治疗(T1)组、法安明小剂量治疗(T2)组。于应用法安明前、后第4、8、12周分别测定4组大鼠的体重、尿蛋白总量(24h)、尿白蛋白(24h),血肌酐;检测大鼠血P-选择素、肾组织P-选择素及P-选择素mRNA表达。结果:与N组比较,DN组大鼠肾重/体重指数以及24h尿微量白蛋白、蛋白定量、血肌酐均显著上升(P<0.05),肾组织P-选择素mRNA和蛋白表达增强(P<0.05)。与DN组比较,T1组大鼠、肾重/体重指数下降(P<0.05),T1和T2组尿蛋白量(24h)、微量白蛋白和血肌酐均显著下降(P<0.01)。T1和T2组P-选择素mRNA表达水平显著下降(P<0.01)。结论:P-选择素可能参与了糖尿病的发病过程,法安明可能通过抑制P-选择素的表达从而对肾脏有保护作用。

The effect of P-seletin on the pathogenesis of type 1 diabetic nephropathy in rats

Objective To investigate the effect of P-selectin on the pathogenesis of diabetic nephropathy (DN) and the renoprotective action of fragmin,a low molecular weight haperin. Methods The murine model of type 1 diabetes was established by intraperitoneal injections of streptozotocin. Rats were divided into normal control group (N group),group with diebetic nephropathy (DN group),high-dose fragmin group (T1 group),and low-dose fragmin group (T2 group). The body weight,24-hour urinary protein and albumin excretion,and serum creatinine (Scr) were measured before and 4,8,and 12 weeks after the use of fragmin. Levels of P-selectin expression were detected by ELISA,immunohistochemistry,and real-time PCR. Results As compared with N group,the body weight,kidney / body weight (KW / BW) ratio,24-hour urinary protein and albumin excretion,and Scr were markedly increased (P < 0.05),and both P-selectin mRNA and protein expression in the renal tissue were significantly enhanced P< 0.05,respectively) in DN group. The KW / BW ratio was declined in T1 group,and 24-hour urinary protein and albumin excretion,Scr,and P-selectin mRNA expression were evidently decreased in both T1 and T2 group (P< 0.01 for all comparisons),as compared to DN group. Conclusions P-selectin may be involved in the pathogenesis of diabetic nephropathy. Fragmin may play a renoprotective role partially through down-regulating the expression of P-selectin.