脂氧素A4对TGF-β1诱导的人肺成纤维细胞增殖、分化的影响及机制  

Effect of lipoxin A4 on transformation growth factor beta-1-induced proliferation and differentiation in human lung fibroblasts and its mechanism

作　　者：王亚群 饶胜芳 周晓燕[1] 黄永红[1] WANG Yaqun;RAO Shengfang;ZHOU Xiaoyan;HUANG Yonghong(Department of Pathophysiology,Basic Medical College of Nanchang University,Nanchang,Jiangxi 330006,China;Graduate College of Nanchang University,Nanchang,Jiangxi 330031,China;Department of Nuclear Medicine,Nanchang University Hospital,Nanchang,Jiangxi 330006,China)

机构地区：[1]南昌大学基础医学院病理生理教研室,330006 [2]南昌大学研究生院,330031 [3]南昌大学医院核医学科,330006

出　　处：《重庆医学》2020年第9期1381-1386,共6页Chongqing medicine

基　　金：国家自然科学基金项目(81660163);江西省自然科学基金项目(20151BAB205002,20161BAB205205);江西省卫生和计划生育委员会中医药科研课题(2016A059)。

摘　　要：目的探讨脂氧素A4对转化生长因子-β1(TGF-β1)诱导的人胚肺成纤维细胞(HFL-1)增殖、分化的影响及其分子机制。方法将体外培养的HFL-1细胞分为3组,即对照组、TGF-β1组、TGF-β1+脂氧素A4组(联合组)。采用细胞计数试剂盒检测24、48、72 h时各组细胞增殖能力;实时荧光定量PCR和Western blot法分别观察各组细胞α-平滑肌肌动蛋白(α-SMA)、I型胶原蛋白(COL-1)的mRNA和蛋白表达水平;Western blot法检测磷酸化核因子E2相关因子2(p-Nrf2)、总Nrf2及其下游抗醌氧化还原酶1(NQO1)、血红素氧合酶-1(HO-1)的蛋白表达水平。结果与对照组比较,TGF-β1组在24、48、72 h时细胞的增殖能力均明显增强(P<0.05),α-SMA、COL-1的mRNA和蛋白表达水平均明显增加(P<0.01),p-Nrf2、NQO1、HO-1的蛋白表达水平均明显下调(P<0.05)。而与TGF-β1组比较,联合组在24、48、72 h时细胞的增殖能力均明显减弱(P<0.05);α-SMA、COL-1的mRNA和蛋白表达水平均明显降低(P<0.01),p-Nrf2、NQO1、HO-1的蛋白表达水平均明显升高(P<0.05)。结论脂氧素A4可抑制TGF-β1诱导的HFL-1细胞的增殖与分化,且该作用可能是通过调节Nrf2通路而实现。Objective To investigate the effect of lipoxin A4 on the transformation growth factor beta-1(TGF-β1)-induced proliferation and differentiation in human embryonic lung fibroblast(HFL-1)and its mechanism.Methods The in vitro cultured human embryonic lung fibroblasts HFL-1 were divided into three groups,including the control group,TGF-β1 group and TGF-β1+lipoxin A4 group(combined group).The cellular proliferative ability in each group was detected by adopting the cell counting kit at 24,48,72 h respectively.The mRNA and protein expression ofα-SMA and type I collagen(COL-1)in each group were observed by adopting the fluorescent quantitative real-time PCR and Western blot methods.The protein expression of phosphorylated Nrf2(p-Nrf2),total Nrf2 and its downstream quinine-resistant oxidoreductase 1(NQO1)and heme oxygenase-1(HO-1)were detected by using Western blot.Results Compared to the control group,the cellular proliferative ability of HFL-1 cells in the TGF-β1 group was significantly increased(P<0.05).Moreover,the mRNA and protein expression levels ofα-SMA and COL-1 were increased(P<0.01),but the p-Nrf2,NQO1 and HO-1 protein expression levels in the TGF-β1 group were down-regulated(P<0.05).Compared with TGF-β1 group,the proliferation capacity of cells at 24,48,72 h in the combination group was significantly decreased(P<0.05).The mRNA and protein expression levels ofα-SMA and COL-1 were significantlydecreased(P<0.01),while protein expression levels of p-nrf2,NQO1 and ho-1 were significantly increased(P<0.05).Conclusion Lipoxin A4 can inhibit TGF-β1-induced proliferation and differentiation of HFL-1 cells,moreover this effect may be realized by regulating Nrf2 pathway.

关 键 词：脂氧素A4 肺成纤维细胞 核因子E2相关因子2 细胞增殖 细胞分化 

分 类 号：R310.4710[医药卫生—基础医学]