氯沙坦对实验性糖尿病大鼠肾脏的炎症抑制作用

目的：观察氯沙坦对糖尿病大鼠肾脏的炎症抑制作用。方法：采用链脲佐菌素（streptomtoein，STZ）65mg／kg腹腔注射建立糖尿病大鼠模型。试验分正常对照组、模型组、治疗组，后一组于模型成功后1周给予氯沙坦20mg／kg灌胃，共12周。分别测定3组24h尿蛋白排泄量、血肌酐、肾重／体重、血浆C反应蛋白（CRP）及肿瘤坏死因子-α（TNF-α）水平；观察肾脏病理形态学变化；应用免疫组化法检测肾组织T011样受体4（TLR4）、核因子-κB（NF-κB）的蛋白表达；RT-PCR检测肾组织TLR4的核酸表达。结果：模型组与对照组相比：模型组大鼠24h尿蛋白、血肌酐、尿素氮、肾重／体重明显升高，肾小球肥大，细胞增生，PAS阳性物质沉积增多；血CRP、TNF-α含量及肾组织TLR4、NF-κB的表达明显增加。经氯沙坦治疗后大鼠血CRP、TNF-α含量下降，肾组织TLR4、NF-κB的表达亦减弱，治疗前后比较存在差异（P〈0．05）。结论：氯沙坦对糖尿病肾病具有保护作用，其作用机制还可能是通过下调NF-κB、TLR4的表达，降低血浆CRP、TNF-α含量，抑制炎症反应而减少糖尿病肾病损伤。

Anti-inflammation Effect of Losartan on Experimental Diabetic Nephropathy in Rats

Objective： To study observe the antiinflammation depressant effect of losartan on experimental diabetic nephropathy in rat, Methods：SD rats were randomly divided into three groups： control group, model group and loeartantreatment group. Rat diabetic nephropathy was induced by intrapefitoneal injection of 65 mg/kg streptozoticin （STZ）, After STZ injection, 20 mg·kg^-1·d^-1 of losartan was given by intragastric administration for 1 week in losartantreatment group. 24 h urine protein, serum creatinine, urea nitrogen, profile of kidney hypertrophy （KW/BW） and the plasma concentration of CRP and TNF- a were determined at week 12. The expression of TLR4 and NF-κB in the kidney was assessed by immunohistochemistry. Results：Compared with control group, the 24 h urine protein, serum creatinine, KW/BW, plasma concentration of CRP and TNF-α and the expression of TLR4 and NF-κB in renal tissue increased in diabetic rats at week 12. Losartan decreased the level of creatinine, the plasma concentration of CRP and TNF -α and the expression of TLR4 and NF-κB in renal tissue of diabetic rats （P〈0.05）. Conelusion： Losartan can reduce the renal lesions in diabetic nephropathy through down - regulating the expression of renal TLR4 and NF- κB, decreasing plasma CRP and TNF-α concentration and inhibiting inflammatory reaction.