摘要
目的探讨福辛普利(FOS)对脂多糖(LPS)诱导的人肾小管上皮细胞(HK-2)增殖及对转化生长因子β激活激酶(TAK1)表达的影响。方法体外培养正常HK-2细胞,分为3组:对照组(Ctrl)、LPS诱导组(10μg/L)、FOS干预组(LPS 10μg/L+FOS 1×106mol/L)。细胞培养12、24和48 h,以甲基噻唑基四唑(MTT)法检测细胞增殖情况,酶联免疫吸附(ELISA)法观察细胞上清纤维黏连蛋白(FN)变化,Western blot法检测TAK1、FN蛋白表达,实时荧光定量PCR检测TAK1 mRNA的含量。结果 LPS诱导组较对照组细胞的增殖水平(在48 h分别为0.462±0.013及0.363±0.014)、胞质中FN的含量均显著增高,且自12 h开始TAK1蛋白(在48 h分别为1.627±0.101及0.547±0.010)及mRNA表达水平上调(P<0.01,P<0.05),FOS干预组细胞增殖(在48 h为0.396±0.011)、FN的含量及TAK1的表达(在48 h蛋白表达为1.308±0.097)较同时间点LPS组(在48 h蛋白表达为1.627±0.101)显著下调(P<0.01)。结论FOS可能通过抑制HK-2的增生与活化,减轻细胞外基质FN的沉积,起到延缓肾间质纤维化的作用。
Objective To investigate the effects of fosinopril(FOS) on expression of TAK1 and proliferation of the human renal tubular epithelial cells induced by LPS. Methods Human renal tubular epithelial (HK-2) cells were divided into three groups: blank control group(Ctrl), LPS group (10μg/L), FOS group (LPS 10μg/L + FOS 1 × 106 mol/L). At 12, 24, 48 hours, HK-2 proliferation was detected by methyl thiazolyl tetrazolium (MTF) as- say. The change of fibronectin (FN) in the supernatants of the cultured HK-2 was detected by enzymelinked immu- nosorbent assay (ELISA). The protein expressions of TAK1 and FN were measured by Western blot. The mRNA expressions of TAK1 was measured by real-time quantitative PCR. Results The cell proliferation and the expres- sion of FN were increased, and the expressions of protein and mRNA of TAK1 in LPS group were upregulating sig- nificantly compared with control group from 12 h (P 〈 0. 01, P 〈 0.05 ), but they were downregulating in FOS group compared with LPS group ( P 〈 0. 01 ). Conclusions FOS probably delays renal interstitial fibrosis by inhibiting proliferation and activation of HK-2 and decreasing accumulation of extracellular matrix.
出处
《基础医学与临床》
CSCD
北大核心
2012年第9期1088-1092,共5页
Basic and Clinical Medicine
作者简介
通信作者(correspondingauthor):lsylushouyan@163.com