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目的:观察心脏收缩力调节(CCM)对慢性心力衰竭(心衰)兔心肌重构的影响并探讨其可能机制。方法:选取新西兰大白兔30只,分为假手术组、心衰组、心衰+CCM组,各组均n=10。假手术组仅开胸,未行升主动脉套扎。心衰组、心衰+CCM组通过升主动脉根部套扎法建立兔慢性心衰模型,心衰+CCM组模型制作成功后给予4周的CCM治疗。分别于实验第12周末和(或)第16周末对各组实验动物,采用超声心动图检测心脏功能,Masson染色评价心肌组织纤维化及病理形态改变,采用酶联免疫吸附法(ELISA)检测血浆B型利钠肽(BNP)水平,蛋白免疫印迹(Westernblot)法检测心肌组织I型胶原蛋白、Ⅲ型胶原蛋白、基质金属蛋白酶(MMP)2、MMP9、MMP抑制因子(TIMP)1、半乳糖凝集素3蛋白表达水平。结果:(1)超声心动图结果:实验第12周末与假手术组相比,心衰组、心衰+CCM组左心室收缩末内径(LVESD)、左心室舒张末内径(LVEDD)明显扩大,左心室缩短率(LVFS)和左心室射血分数(LVEF)明显下降(P<0.05);实验第16周末,与心衰组相比,心衰+CCM组的LVESD、LVEDD、LVEF、LVFS指标明显改善(P<0.05)。(2)病理学改变:Masson染色示与假手术组相比心衰组心肌组织胶原纤维含量明显增加(P<0.05),CCM可部分减轻心衰心肌组织的胶原纤维沉积(P<0.05)。(3)实验第12周末,与假手术组相比,心衰组、心衰+CCM组血浆BNP水平明显升高(P<0.05)。实验第16周末,与心衰组相比,心衰+CCM组的血浆BNP水平下降,但仍高于假手术组(P<0.05)。(4)Western blot法检测结果:心衰组心肌组织中I型胶原蛋白、Ⅲ型胶原蛋白、MMP2、MMP9、TIMP1、半乳糖凝集素3的蛋白表达水平明显高于假手术组(P<0.05),心衰+CCM组心肌组织中I型胶原蛋白、Ⅲ型胶原蛋白、MMP2、MMP9、TIMP1、半乳糖凝集素3的蛋白表达水平较心衰组明显下降(P<0.05),但仍高于假手术组(P<0.05)。结论:心脏收缩力调节可以改善慢性心衰兔心功能及心肌重构,其机制可能与下调心衰心肌组织中I型胶原蛋白、Ⅲ型胶原蛋白、MMP2、MMP9、TIMP1、半乳糖凝集素3蛋白的表达有关。
Objective: To observe the effects of cardiac contractility modulation (CCM) on myocardial remodeling in rabbits with chronic heart failure (CHF) and to explore its possible mechanism. Methods: Thirty New Zealand white rabbits were selected and divided into sham operation group, heart failure group and heart failure + CCM group, n = 10 in each group. Sham operation group only thoracotomy, ascending aortic ligation. Heart failure group, heart failure + CCM group established rabbit chronic heart failure model by ligation of the ascending aorta root, CCM group treated with CCM after heart failure + CCM model was successfully established. At the end of the twelfth and / or the twelfth week of the experiment, the cardiac function of each experimental group was examined by echocardiography, the fibrosis and pathological changes of myocardium were evaluated by Masson staining, and the plasma B-type natriuretic peptide (BNP) and Western blotting were used to detect the expression of type I collagen, type III collagen, matrix metalloproteinase (MMP) 2, MMP9, MMP inhibitor 1 Lectin 3 protein expression levels. Results: (1) Echocardiographic results: Left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) in heart failure group and heart failure + CCM group were significantly increased at the end of the twelfth week compared with the sham operation group Left ventricular ejection fraction (LVFS) and left ventricular ejection fraction (LVEF) decreased significantly (P <0.05). At the end of the 16th week, LVESD, LVEDD, LVEF and LVFS were significantly higher in HF + CCM group than those in HF group Significant improvement (P <0.05). (2) Pathological changes: Masson staining showed that compared with sham-operation group, the content of collagen fibers in heart failure group was significantly increased (P <0.05). CCM could partially reduce the collagen deposition in heart failure myocardial tissue (P <0.05). (3) At the end of the twelfth week, plasma BNP levels in heart failure group and heart failure + CCM group were significantly higher than those in sham operation group (P <0.05). At the end of the 16th week, BNP level in heart failure + CCM group decreased compared with heart failure group, but still higher than that in sham operation group (P <0.05). (4) Western blot results showed that the protein expression of type I collagen, type III collagen, MMP2, MMP9, TIMP1 and galectin-3 in heart failure group was significantly higher than that in sham operation group (P <0.05 ), The protein expression of type I collagen, type III collagen, MMP2, MMP9, TIMP1 and galectin-3 in heart failure + CCM group was significantly lower than that in heart failure group (P <0.05) In sham operation group (P <0.05). CONCLUSION: Cardiac contractility can improve cardiac function and myocardial remodeling in CHF rats. The mechanism may be related to down-regulation of type I collagen, type III collagen, MMP2, MMP9, TIMP1, galectin-3 Protein expression.