LOX-1介导ox-LDL诱导大鼠系膜细胞表达TGF-β_1及分泌细胞外基质  

Oxidized low density lipoprotein-induced expression of transforming growth factor beta 1 and production of extracellular matrix in rat glomerular mesangial cells is mediated by lectin-like oxidized low density lipoprotein receptor-1

作　　者：杜月光[1] 柴可夫 万海同 

机构地区：[1]浙江中医药大学基础医学院病理生理学教研室,杭州310053 [2]中医临床基础教研室,杭州310053

出　　处：《第二军医大学学报》2007年第8期846-849,共4页Academic Journal of Second Military Medical University

基　　金：浙江省自然科学基金(M303727)~~

摘　　要：目的:观察氧化低密度脂蛋白(ox-LDL)对大鼠肾小球系膜细胞表达血凝素样氧化低密度脂蛋白受体1(LOX-1)、转化生长因子β_1(TGF-β_1)及分泌细胞外基质(ECM)的影响,并观察LOX-1抑制剂多聚肌苷酸(PIA)对ox-LDL上述作用的影响。方法:体外培养肾小球系膜细胞,RT-PCR检测不同浓度(0、25、50、100μg/ml)ox-LDL组肾小球系膜细胞LOX-1 mRNA的表达;RT-PCR观察空白组、ox-LDL组(50μg/ml)和PIA组(50μg/ml ox-LDL+250μg/ml PIA)肾小球系膜细胞LOX-1、TGF-β_1 mRNA的表达,ELISA法检测上述3组肾小球系膜细胞培养上清中TGF-β_1、纤连蛋白(FN)、Ⅳ型胶原(ColⅣ)的含量。结果:RT-PCR结果表明,25、50、100μg/ml ox-LDL组LOX-1 mRNA表达明显高于0μg/ml组(P<0.05),其中50μg/ ml组表达最高;50μg/ml ox-LDL组肾小球系膜细胞LOX-1、TGF-β_1 mRNA表达明显高于空白组和PIA组(P<0.01)。ELISA结果表明50μg/ml ox-LDL组肾小球系膜细胞培养上清中TGF-β_1、FN、ColⅣ的含量明显高于空白组和PIA组(P<0.05)。结论:ox-LDL体外可促进大鼠肾小球系膜细胞表达LOX-1、TGF-β_1及分泌细胞外基质,PIA可抑制ox-LDL的上述作用,提示LOX-1可能介导了ox-LDL对肾小球系膜细胞的损伤,参与了肾小球硬化的发生和发展。Objective： To investigate the effect of oxidized low-density lipoprotein （ox-LDL） on expression of lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1）, transforming growth factor beta I（TGF-β1 ）, and secretion of extracelluar matrix （ECM）in cultured rat glomerular mesangial cells （GMCs）, and to investigate the influence of LOX-1 inhibitor polyinosinic acid （PIA） on the effect of ox-LDL. Methods： Rat gtomerutar masengiat cells were cultured in vitro. RT-PCR was employed to determine the LOX-1 mRNA expression in GMCs incubated with different concentrations of ox-LDL （0, 25, 50, 100 μg/ml）. The expression of LOX-1 and TGF-β1 mRNA was also determined by RT-PCR in the blank control group, ox-LDL （50 μg/ml）group and PIA（50 μg/ml ox-LDL＋250 μg/ml PIA）group. The contents of TGF-β1 ,fibronectin （FN）, and collagen Ⅳ （Col Ⅳ） in the supernatants of the above 3 groups were determined by ELISA. Results： RT-PCR showed that LOX-1 mRNA expression in 25, 50 and 100 μg/ml ox-LDL groups was significantly higher than that of blank control group（P〈0.05）, with the highest expression found in the 50 μg/ml ox-LDL group; the expression of LOX-1 and TGF-β1 mRNA was significantly higher in 50 μg/ml ox-LDL group than that in the other 2 groups （P〈0.01）. ELISA results demonstrated that the supernatant contents of TGF-β1 ,FN and Col Ⅳ were significantly higher in 50 μg/ml ox-LDL group than those in the other 2 groups （P〈 0.05）. Conclusion： Ox-LDL can upregulate the expression of LOX-1 and TGF-β1 mRNA and the secretion of extracelluar matrix in GMCs. Polyinosinic acid can antagonize the above effect of ox-LDL, suggesting that LOX-1 may participate in ox-LDL- induced GMCs damage and is involved in the development and progression of glomerulosclerosis.

关 键 词：糖尿病肾病 肾小球硬化 氧化低密度脂蛋白 血凝素样氧化低密度脂蛋白受体1 转化生长因子β1 细胞外基质 

分 类 号：R587.2[医药卫生—内分泌]