心脏收缩力调节对转化生长因子β1/结缔组织生长因子信号通路的影响

摘要

Objective To study the effect of cardiac contractility modulation (CCM) on TGFβ1/Smad/CTGF signaling pathway.Methods A rabbit heart failure (HF) model was established by ligating the ascending aortic root.Thirty rabbits were divided into sham operation group (n=10),HF group (n=10) and CCM group (n=10).Myocardial tissue collagen Ⅰ and collagen Ⅲ were analyzed with Sirius red staining,myocardial tissue hydroxyproline level was measured by chromometry,and expressions of TGFβ1,Smad3,Smad7,CTGF were detected by Western blot in 3 groups.Results Collagen Ⅰ,collagen Ⅲ and hydroxyproline content were highcr in HF group than in sham operation group,while collagen Ⅰ,collagen Ⅲ and hydroxyproline conten were lower in CCM group than in sham operation group (0.69±0.05 μg/mg vs 0.98±0.04 μg/mg,P＜0.05).The expression levels of TGFβ1,Smad3,CTGF were higher while those of Smad7 were lower in HF group than in sham operation group (P＜0.05).The expression levels of TGFβ1,Smad3,CTGF were lower while those of Smad7 were higher in CCM group than in HF group (0.49±0.03 vs 0.67±0.04,0.43±0.06 vs 0.59±0.06,0.45±0.08 vs 0.75±0.09,P＜0.05;0.43±0.08vs 0.26±0.04,P＜0.05).Conclusion CCM can improve the myocardial fibrosis in HF rabbits by downregulating the expression of TGFβ1,Smad3,CTGF and upregulating the expression of Smad7.%目的 观察心脏收缩力调节(CCM)对心力衰竭(心衰)兔转化生长因子β1(TGFβ1)/Smad/结缔组织生长因子(CTGF)信号通路影响.方法 30只新西兰大白兔经升主动脉根部套扎建立心衰模型,分为假手术组、心衰组、CCM组(心衰模型成功后,给予4周CCM治疗),每组10只.采用天狼猩红染色法分析心肌组织Ⅰ型及Ⅲ型胶原纤维;比色法测定心肌组织羟脯氨酸含量;蛋白印迹法检测心肌组织TGFβ1、Smad3、Smad7、CTGF蛋白表达水平.结果 与假手术组比较,心衰组Ⅰ型和Ⅲ型胶原纤维及羟脯氨酸含量增加(P＜0.05),CCM组较心衰组减轻心肌Ⅰ型和Ⅲ型胶原纤维及羟脯氨酸含量[(13.19±5.96)％ vs (16.31±7.01)％,(7.39±2.13)％ vs (11.57±5.02)％,(0.69±0.05)μg/mg vs(0.98±0.04)μg/mg,P＜0.05].与假手术组比较,心衰组TGFβ1、Smad3、CTGF蛋白表达升高,Smad7蛋白表达下降(P＜0.05).与心衰组比较,CCM组TGFβ1、Smad3、CTGF蛋白表达下调(0.49±0.03 vs0.67±0.04,0.43±0.06 vs0.59±0.06,0.45±0.08 vs 0.75±0.09,P＜0.05),Smad7蛋白表达上调(0.43±0.08 vs 0.26±0.04,P＜0.05).结论 CCM可下调TGFp1、Smad3、CTGF蛋白表达,上调Smad7蛋白表达,改善心衰兔心肌纤维化.