体外心脏震波治疗促进梗死心肌血管再生和抑制心肌纤维化的机制研究  

Mechanism of extracorporeal cardiac shock wave therapy on promoting angiogenesis and inhibiting myocardial fibrosis in infarcted myocardium in rats

作　　者：刘利萍[1] 张雅文 叶雨佳 宋文娟 马雪娟[1] 谷颖[1] 赵月 孙钺[1] 王钰[1] Liu Liping;Zhang Yawen;Ye Yujia;Song Wenjuan;Ma Xuejuan;Gu Ying;Zhao Yue;Sun Yue;Wang Yu(Department of Cardiology,First Affiliated Hospital of Kunming Medical University,Kuming 650032,China)

机构地区：[1]昆明医科大学第一附属医院心内科,650032

出　　处：《中国心血管杂志》2023年第3期262-269,共8页Chinese Journal of Cardiovascular Medicine

基　　金：云南省科技厅-昆明医科大学应用基础研究联合专项基金(2018FE001)。

摘　　要：目的探讨急性心肌梗死(AMI)大鼠经体外心脏震波治疗(CSWT)后心肌缺血和心功能改善与外周血内皮祖细胞(EPCs)、基质细胞衍生因子1(SDF-1)和转化生长因子β1(TGF-β1)的相关性,以揭示CSWT促血管生成机制。方法采用随机数表法将20只SD大鼠分为假手术+CSWT组(5只)、AMI组(5只)和AMI+CSWT组(10只)。假手术+CSWT组仅开胸,其他两组构建AMI模型。假手术+CSWT组和AMI+CSWT组均行9次CSWT治疗[能量:0.09 m J/mm^(2),次数:900次,频率:3 Hz(3次/s)]。各组均在术前和术后1 d、30 d抽取外周静脉血检测SDF-1、TGF-β1含量和EPCs集落数,并于术后5 d、30 d实施超声心电图检测左室射血分数(LVEF)。术后30 d行心脏组织取材,分别采用HE染色、Masson染色评估心肌组织病理形态学改变及心肌纤维化程度;于心肌梗死边缘区检测TGF-β1蛋白含量,Ⅷ因子免疫组化染色计数心肌毛细血管密度。结果(1)术前,三组间的EPCs、SDF-1和TGF-β1含量均无统计学差异(均为P>0.05)。(2)各组观察期内EPCs、SDF-1随时间推移呈上升趋势;术后1 d,假手术+CSWT组EPCs明显高于AMI组、AMI+CSWT组[(0.71±0.08)×10^(-3)%比(0.52±0.04)×10^(-3)%、(0.61±0.07)×10^(-3)%,均为P<0.05];术后30 d,三组间的EPCs无统计学差异(P>0.05)。(3)术后1 d和30 d,假手术+CSWT组的SDF-1明显低于其他两组(均为P<0.05);术后30 d,AMI+CSWT组的SDF-1明显高于AMI组[(203.80±110.13)ng/ml比(127.82±19.61)ng/ml,P=0.012]。(4)术后1 d,AMI组和AMI+CSWT组的TGF-β1含量均较术前明显增加(均为P<0.05);术后30 d,除AMI组外,其他两组的TGF-β1含量较术后1 d均降低,且假手术+CSWT组、AMI+CSWT组明显低于AMI组[(37448.72±7987.74)ng/ml、(38402.03±8993.55)ng/ml比(56844.75±8311.27)ng/ml,均为P<0.05]。(5)与AMI组相比,AMI+CSWT组的心肌结构虽有破坏,但细胞水肿程度较轻,局部可见完整心肌和新生血管排列,心肌纤维化程度较轻,TGF-β1蛋白含量明显降低,心肌毛细血管密度高。(6)�Objective To investigate the correlation between the improvement of myocardial ischemia and cardiac function after extracorporeal cardiac shock wave therapy(CSWT)and peripheral blood endothelial progenitor cells(EPCs),stromal cell-derived factor-1(SDF-1),transforming growth factor-β1(TGF-β1)in rats with acute myocardial infarction(AMI),and to reveal the mechanism of CSWT promoting angiogenesis.Methods Twenty male SD rats were divided into sham operation+CSWT group(n=5),AMI group(n=5)and AMI+CSWT group(n=10).AMI model was constructed by ligation of left anterior descending(LAD)artery after thoracotomy.Rats in sham operation+CSWT group did not undergo LAD ligation.AMI+CSWT group and sham operation+CSWT group were treated with CSWT[energy:0.09 mJ/mm^(2),number:900 times,frequency:3 Hz(3 times/s)].Peripheral blood was extracted before surgery and on the 1^(st) and 30^(th) day after surgery for EPCs isolation,culture and identification,SDF-1 and TGF-β1 content determination.Echocardiography was performed on the 5^(th) and 30^(th) day after surgery to calculate the left ventricular ejection fraction(LVEF).After the examination of each group,the morphology of myocardial cells was observed by HE staining,the degree of fibrosis was evaluated by Masson staining,the angiogenesis in each area of myocardial infarction was assessed by factorⅧstaining and TGF-β1 protein in the marginal area of myocardial infarction was observed by TGF-β1^(st)aining.Results(1)There was no significant difference in the proportion of EPCs,SDF-1,TGF-β1 within three groups before operation(all P>0.05).(2)EPCs and SDF-1 in the three groups showed an increasing trend over time during the observation period.On the 1^(st) day after surgery,the proportion of EPCs was significantly higher in sham operation+CSWT group compared with AMI group and AMI+CSWT group[(0.71±0.08)×10^(-3)%vs.(0.52±0.04)×10^(-3)%vs.(0.61±0.07)×10^(-3)%,all P<0.05].The proportion of EPCs in three groups did not show significant difference on the 30^(th) day after surger

关 键 词：体外心脏震波治疗 大鼠 急性心肌梗死 血管生成 心肌纤维化 

分 类 号：R542.22[医药卫生—心血管疾病]