雷公藤甲素对糖尿病大鼠肾组织RANTES的影响

Effect of Triptolide on the Expression of RANTES in the Renal Tissue of Diabetic Nephropathy Rats

目的探讨雷公藤甲素(triptolide,TPL)对糖尿病大鼠肾组织的影响及其机制。方法 SD大鼠随机分为正常对照组(正常组)、糖尿病模型组(模型组)、雷公藤甲素小剂量治疗组(TPL小剂量组,TPL0.2 mg/kg灌胃)、雷公藤甲素大剂量治疗组(TPL大剂量组,TPL 0.4 mg/kg灌胃),正常组和模型组给予等量生理盐水灌胃。实验第4、8、12周,各组随机选5只大鼠检测体重、肾重、24 h尿白蛋白(24 hUAL)、FBG、TC、TG、ALT、AST、WBC、HbA1c;采用RT-PCR、ELISA法检测肾皮质调节活化正常T细胞表达与分泌因子(regulated upon activation normal T-cell expressed and secreted,RANTES)蛋白及mRNA表达;HE、PAS、Masson肾组织病理染色,观察各时间点肾小球、肾小管间质病变,PAS染色观察肾小球的硬化指数(glomerular sclerosis index,GSI),计算肾间质纤维化指数(renal interstitial filrosis index,RIFI)。结果与本组4周比较,两个给药组12周24 hUAL、RANTES、GSI、RIFI降低(P<0.01)。与本组8周比较,两个给药组12周24 hUAL、RANTES、GSI、RIFI较本组8周时降低(P<0.05,P<0.01)。与正常组比较,模型组4、8、12周大鼠体重、肾重明显降低(P<0.01),24 hUAL、FBG、TG、TC、HbA1c、RANTES、GSI及RIFI均明显升高(P<0.01)。与模型组比较,两个给药组24 hUAL、RANTES、GSI、RIFI降低(P<0.01)。与TPL小剂量组比较,大剂量组24 hUAL、RANTES、GSI、RIFI降低(P<0.05,P<0.01)。结论雷公藤甲素能抑制糖尿病大鼠肾组织RANTES的过度表达,并可改善肾小球硬化及肾间质纤维化。

Objective To investigate the effect of triptolide （TPL） on the renal tissue of diabetic rats and its possible mechanisms. Methods SD rats were randomly divided into the normal control group （as the normal group）, the diabetic model group （the model group）, the low dose TPL treatment group （the low dose TPL group, TPL 0.2 mg/kg by gastrogavage）, the high dose TPL treatment group （the high dose TPL group, TPL 0.4 mg/kg by gastrogavage）. Equal volume of normal saline was given to rats in the normal group and the model group. Five rats were randomly selected from each group at week 4, 8, and 12 of the experiment to detect body weight, kidney weight, 24 h urinary albumin （24 h UAL）, plasma glucose （FBG）, total cholesterol （TC）, total triglyeride （TG）, alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, white blood cell （WBC）, and hemoglobin Alc （HbAlc）. The mRNA and protein expression of regulated upon activation normal T-cell expressed and secreted （RANTES） in the renal tissue was assessed by reverse transcription-polymerase chain reaction （RT-PCR） and enzyme linked immunosorbent assay （ELISA）. The renal tissue was pathologically stained by HE, PAS, and Masson staining. The glomerular and renal tubular interstitial lesions were observed at each time point. The glomerular sclerosis index （GSI） was observed by PAS staining, and the renal interstitial filrosis index （RIFI） was calcutated. Results Compared with the same group at week 4, the expression of 24 hUAL, RANTES, GSI, and RIFI at week 12 significantly decreased in two TPL groups （P 〈0.01 ）. Compared with the same group at week 8, the expression of 24 h UAL, RANTES, GSI, and RIFI at week 12 also significantly decreased in the two TPL groups （P 〈0.05,P 〈0.01 ）. Compared with the normal group, body weight and the kidney weight obviously decreased at week 4,8, and 12 in the model group （P 〈0.01） ; 24 h UAL, FBG, TG, TC, HbA1c, RANTES, GSI, and RIFI were obviously elevated （P 〈0.01 ）. Compared with the model group, 24 h UAL,, RANTES, GSI, and RIFI also decreased in the two TPL treatment groups （P 〈0.01）. Compared with the low dose TPL group, they were attenuated in the high dose TPL group （P 〈0.05, P 〈0.01 ）.Conclusion TPL could not only inhibit the over-expression of RANTES, but also im- prove the glomerular sclerosis and renal interstitial fibrosis in the renal tissue of diabetic rats.