Exendin-4对肿瘤坏死因子-α诱导的单核细胞趋化蛋白-1表达的影响  

Effect of exendin-4 on monocyte chemoattractant protein-1 expression in cultured rat glomerular mesangial cells induced by tumor necrosis factor-α in vitro

作　　者：江颖娟[1] 薛耀明[1] 张倩[1] 张艳飞[1] 袁园[1] 

机构地区：[1]南方医科大学南方医院内分泌代谢科,广东广州510515

出　　处：《南方医科大学学报》2013年第6期930-933,共4页Journal of Southern Medical University

基　　金：广东省科技计划项目(2009B080701020)

摘　　要：目的观察exendin-4对大鼠肾小球系膜细胞单核细胞趋化蛋白-1(MCP-1)、纤维连接蛋白(FN)表达的影响。方法试验分组:对照组、肿瘤坏死因子-α(TNF-α)组(10 ng/ml)、TNF-α(10 ng/ml)+E1组(1 nmol/L exendin-4)、TNF-α(10 ng/ml)+E5组(5 nmol/L exendin-4)、TNF-α(10 ng/ml)+E10组(10 nmol/L exendin-4)。收集24 h细胞,提取RNA,采用实时荧光定量检测细胞内MCP-1 mRNA的表达;分别在24、48 h收集各组细胞培养上清液,采用ELISA检测培养细胞上清中MCP-1、FN的浓度。结果孵育24 h时,TNF-α组MCP-1 mRNA和细胞培养上清MCP-1、FN表达较对照组明显增加(P<0.01);与TNF-α组比较,TNF-α+E5组、TNF-α+E10组细胞内MCP-1 mRNA和培养上清内MCP-1、FN含量均明显降低;孵育48 h时,TNF-α组细胞培养上清MCP-1、FN表达较对照组明显增加(P<0.01);与TNF-α组比较,TNF-α+E1组、TNF-α+E5组、TNF-α+E10组细胞培养上清内MCP-1、FN含量均明显降低;并且随着时间的延长和exendin-4浓度的增加,培养上清内MCP-1、FN含量降低更加明显。结论 Exendin-4可明显抑制TNF-α诱导的系膜细胞MCP-1 mRNA的表达,并以剂量和时间依赖的方式抑制TNF-α诱导的系膜细胞培养上清内MCP-1、FN的含量,提示exendin-4可能会对肾脏具有一定保护作用。Objective To investigate the effect of exendin-4 on the expression of monocyte chemoattractant protein-1 （MCP-1） and fibronectin （FN） in rat glomerular mesangial cells in vitro. Methods Rat glomerular mesangial cells were divided into 5 groups, namely control group, tumor necrosis factor-α （TNF-a） group （10 ng/ml）, TNF-a （10 ng/ml）＋E1 （1 nmol/L exendin-4） group, TNF-α （10 ng/ml）＋ E5 （5 nmol/L exendin-4） group, and TNF-α （10 ng/ml）＋ El0 （10 nmol/L exendin-4） group. After cultured 24 h or 48 h, RNA were extracted to determine the expression of MCP-1 with real-time PCR, the supernatant were collected to determine the expression of MCP-1 and FN with ELISA. Results Compared with control group, the ceils treated with TNF-a for 24 h showed significantly increase the expression of MCP-1 and FN （P〈0.01）, exendin-4 significantly reduced the expression of MCP-1 and FN in TNF-α＋E5 group and TNF-a＋E10 group （P〈0.05）. After 48h incubation, the expression of MCP-1 and FN increased significantly in TNF-α group （P〈0.01）, which was lowered by exendin-4 in TNF-α＋E1,TNF-α＋E5 and TNF-α＋E10 groups （P〈0.05）. Conclusion Exendin-4 has an intrinsic capability to concentration- and time-dependently inhibit TNF-α-induced expression of MCP-1 and FN in rat mesangial cells, suggesting the beneficial effect of exendin-4 in preventing and treating diabetic nephropathy.

关 键 词：肿瘤坏死因子-Α 单核细胞趋化蛋白-1 纤维连接蛋白 糖尿病肾病 EXENDIN-4 

分 类 号：R587.2[医药卫生—内分泌]