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

Effect of cardiac contractility modulation on TGFβ1/Smad/CTGF signaling pathway

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 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),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TGFβ1、Smad3、CTGF蛋白表达,上调Smad7蛋白表达,改善心衰兔心肌纤维化。

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 higher in HF group than in sham operation group,while collagenⅠ,collagenⅢand hydroxyproline conten were lower in CCM group than in sham operation group（0.69±0.05μg/mg vs 0.98±0.04μg/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±0.08 vs 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.