【摘要】 目的探讨pravastatin(Prav)对血管紧张素Ⅱ(angiotensionⅡ,AngⅡ)诱导的Wistar大鼠心肌成纤维细胞(cardiac fibroblasts,CF)胶原基因表达及其作用机制。方法取1～3日龄Wistar大鼠心室,以酶消化法分离培养大鼠CF。用MTT法测定细胞增殖,RT-PCR方法测定Ⅰ、Ⅲ型前胶原基因(PⅠCP、PCⅢ)表达。将CF分为:(1)空白对照组(A组):不加干预药物;(2)AngⅡ组(B组):AngⅡ10-6 mol/L;(3)Prav+AngⅡ组:在加入AngⅡ10-6 mol/L基础上再分别加入Prav 10-6、10-5、10-4mol/L,分别为C、D、E组;(4)Prav 10-4 mol/L+AngⅡ10-6 mol/L+甲羟戊酸(MVA)10-4 mol/L组(F组);(5)Prav 10-4mol/L+AngⅡ10-6 mol/L+焦磷酸牛龙牛儿基牛龙牛儿酯(GGPP)10-5 mol/L组(G组);(6)Prav 10-4 mol/L+AngⅡ10-6mol/L+焦磷酸法呢酯(FPP)10-5 mol/L组(H组)。结果 Prav呈浓度依赖性的抑制AngⅡ刺激下的CF增殖(P<0.01)。F、G组可完全阻断Prav的抑制作用,与E组比较差异有统计学意义(P<0.01)。H组对Prav的作用无影响(P>0.05)。结论 Prav主要通过抑制甲羟戊酸途径减少成纤维细胞增殖和胶原基因的表达,减缓心肌纤维化过程。更多还原

【Abstract】 Objective To investigate the role of pravastain(Prav) in the proliferation of Wistar rat cardiac fibroblast(CF) and its mechanism.Methods Neonatal Wistar rat cardiac fibroblasts(CF) were isolated and cultured in vitro.The influence of pravastatin on CF proliferation was determined by MTT assay.The mRNA levels of PⅠCP and PCⅢ were detected by RT-PCR.8 groups including(1) group A:the control,(2) group B:AngⅡ(10-6mol/L),(3) group C:Prav(10-6mol/L)+ AngⅡ,(4)group D:Prav(10-5mol/L)+ AngⅡ,(5) group E:Prav(10-4mol/L)+ AngⅡ,(6) group F:Prav(10-4mol/L)+ AngⅡ+ MVA(10-4mol/L),(7) group G:Prav(10-4mol/L)+ AngⅡ+ GGPP(10-5mol/L),(8) group H:Prav(10-4mol/L)+ AngⅡ+ FPP(10-5mol/L).Results Prav could inhibit the CF growth after treated by AngⅡ in a concentration-dependent manner(P<0.01).Group F,G could markedly inhibit the action of Prav attenuating the cell proliferation compared to group E(P<0.01),but group H couldn′t(P>0.05).Conclusion Prav exerted its effect possibly by inhibiting the MVA pathway to decrease fibroblast proliferation and gene expression,which could slow down fibrillation of cardiac muscle.更多还原