Chen Weidong, Chang Baochao, Zhang Yan, Yang Ping, Liu Lei
Department of Nephrology, First Affiliated Hospital, Bengbu Medical College, Anhui 233000, China.
Department of Laboratory, First Affiliated Hospital, Bengbu Medical College, Anhui 233000, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2015 May;31(5):615-9.
To observe the effect of rhein on the expression of SIRT1(Sirtuin 1) in kidney of diabetic rats, and to explore the role of rhein in protecting rat kidney against diabetic nephropathy and possible mechanism.
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 creatinine (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 SIRT1 in renal tissues at protein and mRNA levels, respectively.
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 SIRT1 was negatively correlated with 24 h U-PRO and MGV.
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 SIRT1 expression.
观察大黄酸对糖尿病大鼠肾脏中沉默信息调节因子1（SIRT1）表达的影响，探讨大黄酸在保护大鼠肾脏免受糖尿病肾病损害中的作用及可能机制。
采用高糖高脂饮食联合链脲佐菌素（35mg/kg体重）诱导2型糖尿病大鼠。将75只8周龄雄性SD大鼠随机分为6组：正常组、糖尿病组、低、中、高剂量（50、100、150mg/kg）大黄酸治疗组和10mg/kg吡格列酮治疗组。大鼠每天灌胃给予相应物质1次。第16周结束时，测定空腹血糖（FPG）、空腹胰岛素（FINS）、甘油三酯（TG）、总胆固醇（TC）、血清肌酐（Scr）和24小时尿蛋白（24h U-PRO）。计算肾脏肥大指数（KM/BM）、胰岛素抵抗指数（HOMA-IR）。光镜下采用PAS染色观察肾组织病理变化。用病理图像分析系统测量平均肾小球面积（MGA）和平均肾小球体积（MGV）。分别采用蛋白质印迹法和实时定量PCR法检测肾组织中SIRT1蛋白和mRNA水平的表达。
糖尿病大鼠肾脏中SIRT1表达下调。与糖尿病组相比，各治疗组FPG、FINS、HOMA-IR、TG、TC、Scr、24h U-PRO、KM/BM、MGA和MGV水平显著降低，肾组织病理改变明显改善。与糖尿病组相比，大黄酸治疗组和吡格列酮治疗组SIRT1 mRNA和蛋白表达明显增加。高剂量大黄酸治疗组各项指标改善更明显。相关性分析表明，SIRT1表达与24h U-PRO和MGV呈负相关。
糖尿病大鼠肾组织中SIRT1表达降低。大黄酸可通过改善胰岛素抵抗和血脂异常，增加SIRT1表达减轻糖尿病大鼠肾脏损伤。
