洛伐他汀对大鼠系膜细胞增殖及TGF-β1基因启动子活性的调控

Lovastatin in regulation of mesangial cell proliferation and activity of TGF-β1 promoter in rats

目的:观察洛伐他汀对大鼠系膜细胞增殖及对人TGF-β1基因启动子活性的作用。方法:(1)应用MTT法观察洛伐他汀(10-7、10-6、10-5、10-4mol/L)对大鼠系膜细胞增殖的作用;(2)将不同长度的人TGF-β1基因启动子片段与氯霉素乙酰基转移酶(CAT)报告基因组成重组体phTGF2.14和phTGF1.12,采用脂质体法转染至大鼠系膜细胞中,分别加入不同浓度的洛伐他汀(10-7、10-5mol/L)进行干预,用ELISA方法检测报告基因CAT的活性。结果:(1)不同浓度洛伐他汀对大鼠系膜细胞增殖均有明显的抑制作用,与对照组比较有明显差异(P<0.01)。(2)洛伐他汀浓度为10-7mol/L时对重组体phT-GF2.14及phTGF1.12的表达活性无影响,当增大洛伐他汀浓度为10-5mol/L时对重组体phTGF2.14及phTGF1.12的表达活性有抑制作用,与对照组比较有显著差异(P<0.01)。结论:洛伐他汀能够抑制系膜细胞增殖,当浓度为10-5mol/L时对人TGF-β1基因启动子活性也具有抑制作用。

Objective：To study the effect of lovastatin on the proliferation of rat mesangial cell（RMC） and the activity of TGF-β1 gene promoter. Methods： （1）Effect of lovastatin（10^-2,10^-6 ,10^-3 and 10^-4 mol/L） on proliferation of RMC was analyzed by MTT. （2）Two plasmids（phTGF2.14 and phTGF1. 12） containing various lengths of 5＇flank sequences of human TGF-β1 geneand CAT as reporter gene were constructed and transfected into RMC by FuGENE transfection reagent. The effects of lovastatin （10^-7,10^-5mol/L）on transcription of the 2 plasmids were studied by CAT-ELISA. Results： （1）Different concentrations of lovastatin had obvious inhibitive effects on the proliferation of RMC compared with control group（P〈0.01 ）. （2）Lovastatin at 10^-7mol/L did not inhibit the activities of phTGF2.14 and phTGF1. 19 but at 10^-5mol/Lmarkedlyinhibited the activities of phTGF2.14 and phTGF1. 19 compared with control group（P〈0.01）. Conclusion： Lovastatin has inhibitive effects on the proliferation of RMC and when at 10^-5mol/L lovastatin can also inhibit the activity of TGF-β1 gene promoter.