文档介绍：贞清方调节SREBP-1c减少糖尿病大鼠肾脏脂质沉积
文秀英,1 许明旺,2 胡勤瑾,3 罗琼,3 鲁敏,3
(,武汉430077;
2. 华中科技大学同济医学院附属梨园医院老年医药学研究所;3. 华中科技大学同济医学院硕士研究生)
摘要:目的探讨贞清方对糖尿病大鼠肾脏脂质代谢的调节作用及其分子机制。
方法高糖高脂饲料加低剂量链脲佐菌素注射制备2型糖尿病大鼠模型,将成模大鼠分为:贞清方组、二甲双胍组、模型组,另设正常对照组,每组18只大鼠。分别在治疗8周和12周时检测大鼠的肾皮质TG含量。12周时,采用RT-PCR检测肾皮质固醇调节元件结合蛋白-1c (SREBP-1c)和脂肪酸合成酶(FAS)的mRNA表达,同时,检测血糖、血甘油三酯(TG)、总胆固醇(TC)和尿微量白蛋白排泄率(UAE), 肾脏行HE染色、在光镜下作肾组织形态学观察。结果 8周时模型组肾皮质TG含量有增高的趋势,但与正常组比较无显著性差异(P>),两治疗组的肾皮质TG含量与正常组比较无明显变化。12周时,与正常组相比,模型组大鼠肾皮质TG含量显著升高(P<), 且SREBP-1c和FAS mRNA 的表达明显上调(P<)。贞清方组和二甲双胍组肾皮质TG含量较模型组明显减少(P<)。贞清方组SREBP-1c mRNA的表达非常显著低于模型组(P<),二甲双胍组的SREBP-1c mRNA表达亦低于模型组(P<),但高于正常组(P<)。贞清方组和二甲双胍组的FAS mRNA表达均显著低于模型组(P<)。与模型组比较,两治疗组血糖、TG和UAE明显下降(P<),TC亦下降(P<)。贞清方组和二甲双胍组的肾脏病理改变较模型组减轻。结论贞清方可通过下调糖尿病大鼠肾组织SREBP-1c及其下游基因FAS mRNA的表达,减少肾脏的脂肪沉积,改善肾功能和形态学改变。
关键词:贞清方;糖尿病肾病;固醇调节元件结合蛋白-1c;脂肪酸合成酶
基金项目:国家自然基金资助项目(30672730)
作者介绍:文秀英,女,博士,教授,主任医师。
*通讯作者:许明旺,女,副主任药师,Tel:027-62542635 email:hailen2006@
Zhenqing Recipe Reduce Lipid Accumulation in Diabetic Rat Kidney by Regulating Expression of SREBP-1c mRNA
WEN Xiu-ying, XU Ming-wang,HU Qin-jin,( Liyuan Hospital , Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, China)
ABSTRACT: OBJECTIVE To investigate Zhenqing Recipe(ZQR) in regulation of renal lipid metabolism and its molecular mechanisms. Methods Type 2 diabetic rat model was established with feeding high-glucose and high-fat diet, and injecting low dose streptozotocin. The model rats were divided into: untreated model group, ZQR group, metformin group, normal rats served as control, 18 rats in each group. At week 8 and week 12 after treatment, TG contents in renal cortex were measured. And at week 12, the expression of sterol regulatory element binding-protein- 1c (SREBP-1c ) and fatty acid synthase (FAS) mRNA were detected by RT-PCR. Meanwhile, fasting blood glucose (FBG), total triglyceride (TG) and total cholesterol (TC) and urine albumin excretion (U