法安明对糖尿病大鼠血清及肾组织中P-selectin的作用

目的：探讨P-selectin在糖尿病肾病发病中的作用以及低分子肝素法安明对肾脏保护作用的机制。方法：用链脲佐菌素（STZ60mg/kg体重）构建糖尿病大鼠模型后随机分为糖尿病组（DN组）和法安明治疗组（T组）,并设正常对照组（N组）。于应用法安明前、后第4、8、12周分别测定3组大鼠的体重、24h尿蛋白总量、24h尿白蛋白、Scr,12周测血脂、凝血功能;应用ELISA方法检测各组大鼠血P-selectin水平,用免疫组化方法检测肾组织P-selectin,用real-time PCR法测P-selectin mRNA表达;并观察各组大鼠肾脏组织病理学改变。结果：与N组比较,DN组大鼠肾重/体重指数以及24h尿白蛋白、蛋白定量、Scr均显著上升（P〈0.05）;肾组织P-selectin mRNA和蛋白表达增强（P〈0.01或P〈0.05）。与DN组比较,T组大鼠、肾重/体重指数下降（P〈0.05）、24h尿白蛋白、24h尿蛋白量和Scr均显著下降（P〈0.01）;P-selectin mRNA表达水平显著下降（P〈0.01）。结论：P-selectin可能参与了DN的发病过程,法安明可能通过影响P-selectin的表达从而对肾脏有保护作用。

Effects of Fragmin on Expression of P-selectin in Serum and Renal of Diabetic Nephropathy Rats

Objective：To investigate the role of P- selectin in the progress of diabetic nephropathy（DN） ,and to explore the renal protection mechanism of Fragmin（ low molecular weight haperin） against DN. Methods：The SD rats by intraperitoneal injection of streptozotocin（STZ） were divided into normal control group（N group）, diebetic nephropathy group（DN group） and treatment group（T group）. At week 4,8,and the week 12 with Fragmin,body weight,24 hour urinary protein and albuminuria,serunl creatinine（Scr） were measured,and renal tissue were also observed. Additionally, Lipid level and function of blood coagulation were measured before final dissection of the rats at the 12th week. The expression level of P selectin was examined by ELISA, irnmunohistochemistry and real- time PCR. Results： Body weight, kidney/body weight rario （KW/BW）, 24 - hour albuminuria and urinary protein, Scr of DN group were higher than those of the controlled （ P 〈 0.05）. P - selectin level and protein expression in .serum and kidney tissue of DN and T group were all significantly higher than those of N group （P 〈 0.05）. P - selectin mRNA expression was also obviously higher than the controlled （P 〈 0.01 ）. Body weights, KW/BW, albuminuria, urinary protein of T group rats were lower than those of DN group. P- selectin mRNA expression of T group was also lower than those of DN group （P 〈 0.01 ）. Conclusion： P- selectin may play an important role in the progression of diabetic nephropathy. Fragmin has renal protective effect in diabetic rats, partially through down - regulating the expression of P - selectin.