大黄酸增加2型糖尿病大鼠肾组织SIRT1的表达

Rhein promotes the expression of SIRT1 in kidney tissues of type 2 diabetic rat

目的研究大黄酸对糖尿病大鼠肾组织沉默接合型信息调节因子2同源蛋白1(SIRT1)表达的影响,探讨大黄酸对糖尿病大鼠肾脏损伤的保护作用及可能机制。方法采用高糖高脂饮食联合链脲佐菌素(35 mg/kg体质量)诱导2型糖尿病大鼠模型,分为正常组,糖尿病组,低、中、高剂量(50、100、150 mg/kg)大黄酸治疗组及10 mg/kg吡格列酮对照组。灌胃给药,每日1次。16周末检测大鼠空腹血糖(FPG)、空腹胰岛素(FINS)、甘油三酯(TG)、总胆固醇(TC)、血肌酐(Scr)、24 h尿蛋白(24 h U-PRO);计算肾质量指数(KM/BM)、胰岛素抵抗指数;PAS染色光镜观察肾组织病理形态学的改变;病理图像分析系统分析平均肾小球面积(MGA)及平均肾小球体积(MGV);实时荧光定量PCR检测肾组织SIRT1 mRNA表达;Western blot法检测肾组织SIRT1蛋白表达。结果糖尿病大鼠肾组织SIRT1表达降低。与糖尿病组比较,各治疗组大鼠FPG、FINS、HOMA-IR、TG、TC、Scr、24 h U-PRO、肾质量指数、MGA、MGV显著降低,肾组织病理形态学明显改善;SIRT1 mRNA及蛋白表达显著增加;大黄酸高剂量组各指标改善较显著。相关性分析显示,SIRT1蛋白表达与24 h U-PRO、MGV呈显著负相关。结论糖尿病大鼠肾组织SIRT1表达降低,大黄酸可通过改善胰岛素抵抗和血脂紊乱,增加SIRT1的表达,改善糖尿病大鼠肾脏损害。

Objective To observe the effect of rhein on the expression of SIRTI （ Sirtuin 1） in kidney of diabetic rats, and to explore the role of rhein in protecting rat kidney against diabetic nephropathy and possible mechanism. Methods The type 2 diabetic rats were induced by high-glucose and high-fat diet combined with streptozotocin （35 mg/kg body mass）. Seventy-five eight-week-old male SD rats were randomly divided into 6 groups： normal group, diabetic group, low-, medium- and high-dose （50, 100, 150 mg/kg） rhein treatment groups and 10 mg/kg pioglitazone treatment group. The rats were given corresponding substances intragastrically once a day. At the end of the 16th week, the fasting plasma glucose （FPG）, fasting insulin （FINS）, triglycerides （TG）, total cholesterol （TC）, serum craatinine （Scr） and 24 hours urine protein （24 h U-PRO） were determined. The renal hypertrophy index （KM/BM）, insulin resistance index （HOMA-IR） were calculated. The pathological changes in renal tissues were examined by PAS staining under a light microscopy. The mean glomerular area （MGA） and mean glomerular volume （MGV） were measured by pathological image analysis system. Western blotting and real-time quantitative PCR were used to determine the expression of SIRTI in renal tissues at protein and mRNA levels, respectively. Results The expression of SIRT1 was down-regulated in the kidney of diabetic rats. The levels of FPG, FINS, HOMA-IR, TG, TC, Scr, 24 h U-PRO, KM/BM, MGA and MGV significantly decreased and the histopathology of renal tissues were significantly improved in all treatment groups compared with diabetic group. The expression of SIRT1 mRNA and protein markedly increased in rhein treatment groups and pioglitazone treatment group compared with diabetic group. The indicators in high-dose rhein treatment group were improved more significantly than those in the other groups. Correlation analysis showed that the expression of SIRTt was negatively correlated with 24 h U-PRO and MGV. Conduslon The expression of SIRT1 was reduced in kidney tissues of diabetic rats. Rhein could attenuate kidney damage in diabetic rats by improving the insulin resistance and dyslipidemia, and increasing the SIRT] expression.