氧化低密度脂蛋白对人肾小球系膜细胞A型清道夫受体表达的调节作用

Effects of Oxidized Low-density Lipoprotein on Expression of Type A Scavenger Receptor in Human Mesangial Cells

目的研究氧化低密度脂蛋白(Ox-LDL)对人肾小球系膜细胞(HMC)A型清道夫受体(SR-A)表达的调节作用,探讨在慢性肾脏疾病中Ox-LDL加重肾病进展的作用机制。方法脂质体转染含SR-AcDNA的表达质粒,建立稳定高表达SR-A的人肾小球系膜细胞株(HMCL),油红“O”染色检测HMCL对Ox-LDL的摄取;RT-PCR法检测Ox-LDL和LDL对HMCSR-AmRNA表达的作用。结果稳定高水平表达SR-A的HMCL对Ox-LDL的摄取明显强于未转染细胞;Ox-LDL上调HMCSR-AmRNA的表达,作用于24h达到高峰;Ox-LDL(10～100μg/ml)作用24h对HMCSR-AmRNA的上调作用呈剂量依赖性;天然LDL对SR-A的表达无明显影响。结论在HMC,SR-A是Ox-LDL进入细胞内的主要受体之一,Ox-LDL具有上调HMCSR-AmRNA表达的作用,推测在慢性肾脏疾病进展中,局部沉积的LDL经氧化修饰后可能通过刺激SR-A的表达进入细胞内增强其对HMC的毒性作用,进而加重肾小球硬化的进展。

Objective To explore the regulational effect of oxidized low-density lipoprotein(Ox -LDL)on expression of type A scavenger receptor(SR-A)in human mesangial cells (HMC).Methods HMC line(HMCL)with high expression of SR-A(HMCL-SRA)was established after stable transfection of expressive vector with cDNA encoding SR-A.Uptake of Ox -LDL by HMCL was evaluated using Oil Red“O”staining.SR-A mRNA expression was examined using reverse transcription-polymerase chain reaction(RT-PCR).Results More uptake of Ox -LDL was observed in the HMCL-SRA than that in the untransfected HMCL.Ox -LDL could induce SR-A mRNA expression in HMC in a dose-dependent manner,and reached a peak level after24h of stimulation.After24h of stimulation with Ox -LDL at the dose of10,50and100μg/ml,SR-A mRNA expression was up-regulated to1.35,1.83and2.30-fold of controls,respectively.However,LDL had no effect on the expression of SR-A.Conclusions It suggests that SR-A be a major binding receptor to uptake Ox -LDL in HMC.Ox -LDL may promote the progression of chronic renal diseases through up-regulation of SR-A.