脂肪酸通过固醇调节元件结合蛋白1诱导足细胞的损伤  

Free fatty acid induced podocytes injury by increased SREBP1

作　　者：仇丽茹[1,2] 唐锦辉[1] 周建华[1] Moshe Levi 

机构地区：[1]华中科技大学同济医学院附属同济医院儿科,湖北武汉430030 [2]美国科罗拉多州大学医学院肾脏病研究中心

出　　处：《中国医院药学杂志》2013年第18期1472-1476,共5页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金资助(编号:81070557)

摘　　要：目的:确定脂代谢和固醇调节元件结合蛋白在糖尿病和肥胖相关肾病和足细胞损伤发病机制中的重要作用,为白桦脂醇治疗糖尿病肾病提供理论依据。方法:游离脂肪酸250μm处理分化后的人足细胞48 h,检测足细胞脂滴形成和TLR2/TLR4mRNA和活化的SREBP1以及TLR4的蛋白表达情况以及炎性细胞因子IL-6的mRNA的表达;SREBP1c脂质体转染足细胞,检测足细胞脂滴形成和TLR4和IL-6的表达。结果:游离脂肪酸250μm作用足细胞24 h即诱导人足细胞凋亡,CARS成像显示足细胞脂滴增加,活化的SREBP1的65 kD部分表达增加,TLR2/TLR4的mRNA和TLR4的蛋白表达增加,IL-6的mRNA增加;SREBP1c转染足细胞后,足细胞内脂质合成明显增加,TLR4的蛋白表达上调,IL-6mRNA表达上调。结论:SREBP1表达上调促进足细胞脂质沉积,诱导TLR2/TLR4通路活化,炎性细胞因子IL-6合成增加。SREBP1在2型糖尿病和肥胖肾病足细胞损伤过程中发挥重要作用,为2型糖尿病肾病和肥胖性肾病提供新的治疗靶点。OBJECTIVE To determine the role of lipid metabolism and the sterol regulatory element binding protein I （SREBP1）in obesity and diabetes induced kidney disease, human podocytes treated with free fatty acid. METHODS The hu man podocytes were cultured with free fatty acid and transfected with SREBPlc. Protein level of SREBPIc and TLR4 were mRNA level of TLR2/TLR4 were measured. Proinflammatory cytokines were checked. CARS imaging and Oil Red O meas ured the lipid of podocytes. RESULTS FFA caused podocyte injury and increased the expression of TLR2/TLR4 in culturedhuman podocytes which may be caused by the dysfunction of lipid homeostasis caused by the increasing activated SREBP1. SREBPlc overexpression also could cause lipid accumulation in the podocytes that increased the expression of TLR4 and IL-6. CONCLUSION These studies indicate novel understanding of the pathogenesis of podocytes injury in II type diabetic kidney

关 键 词：足细胞 固醇调节元件结合蛋白 糖尿病肾病 白桦脂醇 

分 类 号：R969[医药卫生—药理学]