TLR4在糖尿病肾病大鼠肾组织中的表达

目的 观察toll样受体4（toll-like receptor 4,TLR4）、白介素-1（interleukin-1,IL-1）在糖尿病肾病（diabetic nephropathy,DN）大鼠模型中的表达变化,并观察厄贝沙坦对糖尿病肾病大鼠肾组织TLR4表达的影响,初步探讨TLR4在糖尿病肾病发生发展中的作用.方法 通过高糖高脂饮食4周＋腹腔注射链脲佐菌素（streptozocin,STZ）构建SD大鼠DN模型.实验分正常对照组（NC组,n=8）,模型对照组（MC组,n=20）,厄贝沙坦治疗组（ARB组,n=20）.在成模后2、4、6、8周分别检测各组大鼠血糖、24,h尿蛋白;于4、8周末取出肾脏行HE染色观察肾组织病理改变,免疫组化检测肾组织TLR4蛋白的表达,酶联免疫吸附测定（enzyme-linked immuno sorbent assay,ELISA）法检测大鼠血清IL-1含量.结果 HE染色示NC组肾小球结构完整,无明显细胞增生,肾小管未见明显异常;MC组和ARB组可见部分肾小管上皮细胞空泡变性,肾小球体积肥大,炎性细胞浸润.免疫组织化学示肾组织TLR4表达MC组、ARB组均以肾小球、肾小管上皮细胞,细胞浆表达为主,ARB组表达较MC组显著增强（P〈0.05）,MC组表达比NC组显著增强（P〈0.05）.ELISA检测示IL-1含量MC组较NC组显著升高（P〈0.05）,ARB组介于NC组与MC组之间,但NC组与ARB组相比差异无统计学意义（P〉0.05）.结论 糖尿病肾病可能通过上调TLR4的表达,进而上调炎性因子IL-1的表达而引起炎性反应,刺激肾脏基底膜增生引起肾小球、肾小管为主的肾脏病变,厄贝沙坦可通过下调TLR4的表达,对糖尿病肾病起到延缓肾功能衰竭的保护作用.

Expression of Toll-like Receptor 4 in Renal Tissues of Rats with Diabetic Nephropathy

Objective To observe the changes in Toll-like receptor 4（TLR4） and interleukin-1 （IL-1） expression and the effect of irbesartan on TI.R4 expression in renal tissues of rats with di- abetic nephropathy（DN）,and to preliminarily investigate the role of TLR4 in the occurrence and development of DN. Methods Sprague-Dawley rats were fed high-fat and high-sugar diet for 4 weeks and were intraperitoneally injected with streptozocin to establish the animal model of DN. Rats were randomly divided into three groups： normal control group （NC group, n = 8）, model control group（MC group,n=20） and irbesartan treatment group（ARB group,n=20）. Blood glu cose and 24 h urine protein were determined at 2,4,6 and 8 weeks after DN induction,and kidneys were removed at 4 and 8 weeks after DN induction. HE staining. TLR4 protein expression was detected Renal pathological changes were observed by by immunohistochemistry. Serum IL-1 levelswere measured by ELISA. Results HE staining showed that rats in NC group had integrated glo merular structure without obvious hyperplasia and renal tubular abnormality. However, vacuolar degeneration of renal tubular epithelial cells,glomerular hypertrophy and inflammatory cell infil tration were observed in MC and ARB groups. Immunohistochemical staining showed that TLR4 was mainly expressed in the cytoplasm of glomerular and renal tubular epithelial cells. Compared with MC group,TLR4 expression decreased in NC group but increased in ARB group（P〈0.05）. Compared with NC group, IL-1 levels increased in MC group（P〈0.05）. There were no significant differences in IL-1 levels between NC group and ARB group（P〈0.05）. Conclusion The DN re nal stimulates basement membrane hyperplasia and causes glomerular and tubular-based renal le sions through up-regulating the expression of TLR4 and IL-1. Irbesartan treatment may delay re nal failure through down-regulating the expression of TLR4 in DN.