肾去交感神经术对慢性心力衰竭大鼠心肌纤维化及结缔组织生长因子表达的影响

目的 观察肾去交感神经术(renal sympathetic denervation,RDN)对心力衰竭大鼠心肌纤维化及心肌组织中结缔组织生长因子(connective tissue growth factor,CTGF)表达的影响,探讨肾去交感神经术治疗心力衰竭的机制。方法 48只SPF级Wistar雄性大鼠分成4组,分别为心力衰竭RDN治疗组(RDN+HF组)、心力衰竭模型组(Sham+HF组)、假手术组(Sham组)及正常对照组,其中RDN+HF组和Sham+HF组分别进行双侧肾交感神经切除或假手术处后用异丙肾上腺素(isoproterenol,ISO)诱导建立大鼠心力衰竭模型,4周后行心脏彩超测左心室舒张末期内径(LVEDD)、舒张末期容积(LVEDV)、左心室射血分数(EF%)及收缩百分率(FS%)评估心功能变化并处死大鼠,留取心脏左心室心肌组织行Masson染色测定心肌胶原容积分数(CVF);免疫组化法检测心肌组织CTGF蛋白表达,RT-qPCR检测左心室心肌CTGFmRNA。结果 与心力衰竭模型组相比,心力衰竭RDN治疗组中反映心室腔扩大的指标LVEDD和LVEDV(LVEDD:0.65±0.02 vs 0.76±0.04,P<0.05;LVEDV:0.77±0.05 vs 0.91±0.04,P<0.05)均明显减小,反映心肌收缩力的指标EF和FS(EF:72.66%±2.82% vs 64.21%±2.50%,P<0.05;FS:32.55%±2.95% vs 25.88%±3.42%, P<0.05)均明显增大,反映胶原含量的指标CVF(13.96%±2.90% vs 59.69%±4.93%,P<0.05)下降,CTGF蛋白表达(4.53±0.75 vs 7.06±0.72, P<0.05)和mRNA相对量(6.95±0.73 vs 10.88±0.85, P<0.05)均减少,但仍高于假手术组(P均<0.05)。结论 肾去交感神经术能够改善心力衰竭大鼠心功能并抑制心肌纤维化的进展,其机制可能与下调CTGF的表达有关。

Effect of Renal Sympathetic Denervation on Cardiac Fibrosis and the Expression of Connective Tissue Growth Factor in Chronic Heart Failure Rats

Objective To investigate the effect of renal sympathetic denervation(RDN)on cardiac fibrosis and the expression of connective tissue growth factor(CTGF)mRNA and protein in left ventricular(LV) myocardium of rats with heart failure and to explore the undedying mechanisms. Methods Male Wistar rats were randomly divided into 4 groups:RDN plus HF,Sham plus HF,Sham and control group(n=12 for each group). Bilateral renal sympathectomy or sham operation were performed in RDN plus HF and sham plus HF groups respectively and myocardial fibrosis in rats with heart failure(HF) was induced by isoproterenol(ISO). Four weeks after the ISO was injected,left ventricular end-diastolic diameter (LVEDD), end-diastolic volume (LVEDV), left ventricular ejection fraction (EF)% and the evaluation of the contraction percentage% (FS) were detected to evaluate the cardiac function.Myocardial collagen volume fraction (CVF) were determined by Masson staining.The expression of CTGF in heart tissue was detected by immunohistochemistry and semi-quantitative real time-polymerase(RT-PCR). Results Compared with HF model group, LVEDD and LVEDV that represent left ventricular chamber size in RDN group were decreased(LVEDD:0.65±0.02 vs 0.76±0.04,P<0.05;LVEDV:0.77±0.05 vs 0.91±0.04,P<0.05), EF and FS that represent left ventricular systolic function were significantly increased (EF:72.66%±2.82% vs 64.21%±2.50%, P<0.05;FS:32.55%±2.95% vs 25.88%±3.42%, P<0.05)were increased, and CVF that represents myocardial collagen content was decreased(13.96%±2.90% vs 59.69%±4.93%, P<0.05), CTGF protein expression (4.53±0.75 vs 7.06±0.72, P<0.05) and the relative amount of mRNA (6.95±0.73 vs 10.88±0.85, P<0.05) were reduced, but still higher than sham group (P<0.05). Conclusion Renal sympathetic denervation can improve cardiac function and prevent cardiac fibrosis in chronic heart failure rats,which may associated with decreasing expression of CTGF in myocardial tissue.