摘要
目的观察氯沙坦对糖尿病大鼠肾组织TOLL样受体4（TLR4）表达的影响。方法采用链脲佐菌素（STZ，65mg·kg^-1）腹腔注射建立糖尿病大鼠模型，将其分为对照组、模型组、治疗组。治疗组在造模成功后1周给予氯沙坦20mg·kg^-1灌胃。12周后测3组24h尿蛋白、血肌酐、肾重／体重、血CRP及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TLR4、核因子-κB（NF-κB）的蛋白表达。结果模型组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的蛋白表达上调。经氯沙坦治疗后，血CRP、TNF-α含量下降，TLR4、NF-κB的表达下调。结论氯沙坦对糖尿病肾病具有保护作用，其作用机制可能是通过下调NF-κB、TLR4的表达，降低血浆CRP、TNF-α含量来实现的。
Objective To observe the effect of TLR4 expression in renal tissue and the inflammation depressant effect of losartan on experimental diabetic rat. Method SD rats were randomly divided into three groups： control group, model group, losartan-treatment group. In latter two groups diabetic nephropathy was induced by intraperitoneal injection with 65 mg·kg^-1 streptozoticin （STZ）. Then,20 mg·kg^-1· d^-1 losartan was continuously given 1 week after STZ injection in losartan-treatment group. 24 h urine protein, creatinine, urea nitrogen, profile of kidney hypertrophy（KW/BW）, the plasma concentration of CRP and TNF-α were determined at week 12 respectively. Renal protein expression of TLR4 and NF-κB were detected by immunohistochemical method. Results After 12 weeks, the 24 h urine protein, creatinine, KW/BW, plasma concentration of CRP and TNF-α, expression of TLR4 and NF-κB in renal tissue increased in diabetic rats, compared with those of control group. Losartan lessened the level of creatinine, plasma concentration of CRP and TNF-α, protein expression of TLR4 and NF-κB in renal tissue of diabetic rats（P〈0. 05）. Conclusions Losartan can reduce the diabetic nephropathy through down regulation of expression of renal TLR4 and NF-κB, decrease of the plasma CRP and TNF-α, and inhibition of inflammatory reaction.
出处
《临床肾脏病杂志》
2007年第2期82-83,I0001,共3页
Journal Of Clinical Nephrology
基金
湖北省自然科学基金（2005ABA175）
