早期体外心脏震波通过抑制TGF-β1-Smad2/3-MMP-9信号通路改善心肌纤维化  

Early extracorporeal cardiac shock wave inhibits myocardial fibrosis by inhibiting TGF-β1-Smad2/3-MMP-9 signaling pathway

作　　者：李纯 王露[1] 叶雨佳 杨妍[1] 宋文娟 马雪娟[1] 刘利萍[1] 谷颍 赵月 孙钺[1] 王钰[1] Li Chun;Wang Lu;Ye Yujia;Yang Yan;Song Wenjuan;Ma Xuejuan;Liu Liping;Gu Ying;Zhao Yue;Sun Yue;Wang Yu(Department of Cardiology,First Affiliated Hospital of Kunming Medical University,Kunming 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》2024年第3期226-232,共7页Chinese Journal of Cardiovascular Medicine

摘　　要：目的 探究急性心肌梗死(AMI)大鼠早期经体外心脏震波治疗(CSWT)后心功能和心肌纤维化改善与转化生长因子β1-细胞信号转导分子2/3-基质金属蛋白酶9(TGF-β1-Smad2/3-MMP-9)信号通路的相关性。方法 采用随机数字表法将30只SD大鼠分为sham、AMI、AMI+CSWT、AMI+SB431542和AMI+SB431542+CSWT组,每组各6只。sham组仅开胸,其他4组构建AMI模型。AMI+SB431542组和AMI+SB431542+CSWT组在术后4d行SB431542处理,持续3d。AMI+CSWT组和AMI+SB431542+CSWT组均行9次CSWT[于术后7d开始行CSWT,两次之间间隔1d,能量:0.09m J/mm~2,一个缺血区域共1800震,频率:3Hz(3震/s)]。各组均在术后4d和62d行超声心动图检测左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)、左心室舒张末期容积(LVEDV)和左心室收缩末期容积(LVESV)。术后62d行心脏组织取材,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-Smad2/3-MMP-9信号通路相关蛋白表达水平及COL-Ⅰ、COL-Ⅲ蛋白表达水平。结果 (1)术后4d,与sham组相比,AMI、AMI+CSWT、AMI+SB431542和AMI+SB431542+CSWT组的LVEF、LVFS明显降低,LVESV明显扩大(均为P<0.05)。(2)术后62d,与sham组相比,AMI组的LVEF、LVFS明显降低,LVEDV、LVESV明显扩大(均为P<0.05);与AMI组相比,AMI+CSWT组的LVEF、LVFS明显改善,LVEDV、LVESV明显回缩(均为P<0.05);与AMI+CSWT组相比,AMI+SB431542+CSWT组的LVEF、LVFS、LVEDV和LVESV无统计学差异(均为P>0.05)。(3)HE染色显示,AMI组较sham组红色区域排列紊乱、蓝色区域增多;AMI+CSWT组较AMI组红色区域排列整齐、蓝色区域减少,但较sham组蓝染区域增多。(4)Masson染色显示,与sham组相比,AMI组胶原容积分数(CVF)明显升高(P<0.001);与AMI组相比,AMI+CSWT和AMI+SB431542组的CVF明显降低(均为P<0.05);与AMI+CSWT组相比,AMI+SB431542+CSWT组CVF较高,但无统计学差异(P=0.65)。(5)Westernblot结果显示,与sham组相比,AMI组的TGF-β1、Smad3、MMP-Objective To investigate the correlation between the improvement of cardiac function and myocardial fibrosis and the transforming growth factor β1-cellular signaling molecule 2/3-matrix metalloproteinase 9(TGF-β1-Smad2/3-MMP-9) signaling pathway in acute myocardial infarction(AMI)rats after early extracorporeal cardiac shock wave therapy(CSWT).Methods Thirty SD rats were divided into sham group,AMI group,AMI+CSWT group,AMI+SB431542 group or AMI+SB431542+CSWT group by using randomized numerical table method with 6 rats in each group.Rats in sham group only received open thorax surgery,and the other 4 groups were constructed with AMI model.Rats in AMI+SB431542 group and the AMI+SB431542+CSWT group were treated with SB431542 for 3 days.The AMI+CSWT group and the AMI+SB431542+CSWT group were treated with 9 times of CSWT(CSWT was performed on the 7~(th) postoperative day with the energy of 0.09 mJ/mm~2,the number of times of CSWT:1800 times,and the frequency of CSWT:3 Hz(3 times/s)).Echocardiography was performed at 4 and 62 d after surgery to detect left ventricular ejection fraction(LVEF),left ventricular short-axis shortening(LVFS),left ventricular end-diastolic volume(LVEDV),and left ventricular end-systolic volume(LVESV) in each group.At 62 d after surgery,cardiac tissue was sampled,and HE staining and Masson staining were used to evaluate the pathological changes in myocardial tissue and the degree of myocardial fibrosis;TGF-β1-Smad2/3-MMP-9 signaling pathway-related protein expression levels and COL-I and COL-Ⅲ protein expression levels were detected in the infarcted border area.Results(1) At 4 d postoperatively,compared with the sham group,LVEF and LVFS were significantly lower and LVESV was significantly enlarged in the AMI group,AMI+CSWT group,AMI+SB431542 group,and AMI+SB431542+CSWT group(all P<0.05).(2) At 62 d postoperatively,LVEF and LVFS were significantly lower and LVEDV and LVESV were significantly enlarged in the AMI group compared with the Sham group(all P<0.05);LVEF and LVFS were significantly

关 键 词：体外心脏震波治疗 大鼠 急性心肌梗死 心脏功能 心肌纤维化 

分 类 号：R542.23[医药卫生—心血管疾病]