心肌球源性干细胞对急性心肌梗死再灌注大鼠的治疗作用及机制研究  

Effect and mechanism of cardiosphere-derived cells in the treatment of rats with acute myocardial infarction ;after reperfusion

作　　者：田学峰[1] 朱贵家[1] 刘思宁[1] 鲁宁[1] 张悦[1] 王政[1] 

机构地区：[1]黑龙江省医院心血管内科,黑龙江省哈尔滨150036

出　　处：《中国基层医药》2017年第2期165-168,I0001-I0004,共8页Chinese Journal of Primary Medicine and Pharmacy

基　　金：黑龙江省卫生和计划生育委员会科研课题（2016-499）

摘　　要：目的：心肌球源性干细胞（CDCs）对急性心肌梗死后再灌注是否有保护作用并未明确，该实验将对此进行研究，并探讨其机制。方法该实验选取7～10周龄的雌性Wistar-Kyoto（WKY）大鼠，诱导心肌缺血45 min，分别于再灌注20 min及120 min向梗死区域周围心肌内各注射CDCs及PBS，观察48 h及2周时，采用心脏彩超检测各组左心室腔的大小，心肌组织中活化的caspase-3蛋白表达水平，通过TUNEL染色检测心肌组织中细胞凋亡情况，通过TTC染色检测各组心肌梗死面积的差异。结果 LAD结扎45 min后再灌注，20 min时分别给予PBS及CDCs注射，20 min组注射CDCs组EF％改变明显优于PBS 组（28％比38％，χ2＝7.340，P＝0．008）；CDCs组坏死包块百分比（6．2％比13．4％，χ2＝4．226，P＝0.002；6．2％比13．5％，χ2＝1.853，P＝0．003）、坏死包块重量（6．2％比13．4％，χ2＝2．220，P＝0．002；6．2％比13．5％，χ2＝3．119， P＝0.003）较PBS组明显减少；CDCs组左室坏死区域百分比较PBS组明显减少（45％比24％，χ2＝4．825，P＝0.008）；PBS组心肌坏死厚度交CDCs组更明显（1．96 mm比1．45 mm，t＝0．897，P＝0．028）；CDCs组MMP8和CXGL7表达较PBS组明显升高（MMP8：0．74比0．56，t＝0．657，P＝0．014；CXGL7：0．44比0．81，t＝0．791， P＝0．010）。结论 CDCs可以通过抑制急性心肌梗死后引起的细胞凋亡来减少心肌梗死的面积，并且可以减少部分炎性细胞因子的表达。Objective To investigate whether cardiosphere-derived cells （CDCs）can protect ischemia-reperfusion in acute myocardial infarction,and to explore its mechanism.Methods 7 -10 week-old female Wistar-Kyoto （WKY）rats were used for all in vivo experiment.Ischemia was induced for 45 min to allow reperfusion. Twenty minutes （or two hours）later,CDCs （or PBS control）were injected into the LV cavity with an aortic cross-clamp.After 48 hours and 2 weeks,representative echocardiography long-axis images of the left ventricular （LV） systolic and diastolic dimensions,the protein level of activated caspase-3 were observed,the apoptosis rate of myo-cardial cells and the infarct area of the heart were determined in those groups.Results Rats underwent 45 minutes of ischemia,followed by either 20 minutes or 120 minutes （delayed injection）of reperfusion prior to infusion of CDCs （cells per 100μL）or PBS control （100μL）into the LV cavity during aortic cross-clamp.Ejection fraction,as meas-ured by echocardiography,was significantly preserved in CDCs-treated animals at 48 hours with a 20 -minute,but not a 120-minute,delay of infusion（28.0% vs 38.0%,χ2 =7.340,P=0.008）.CDCs-treated animals reduced percentage of infarct mass（6.2% vs 13.4%,χ2 =4.226,P=0.002;6.2% vs 13.5%,χ2 =1.853,P=0.003）, infarct mass（6.2% vs 13.4%,χ2 =2.220,P=0.002;6.2% vs 13.5%,χ2 =3.119,P=0.003）treated with PBS control.CDC-treated animals reduced infarct size,relative to those of animals treated with PBS control（45.0% vs 24.0%,χ2 =4.825,P=0.008）,less thinning of the LV anterior wall（1.96mm vs 1.45mm,t=0.897,P=0.028）. Protein expressions of MMP-8 and CXGL7 were elevated in the infarct zone of hearts treated with CDCs（MMP-8：0.74 vs 0.56,t=0.657,P=0.014;CXGL7：0.44 vs 0.81,t=0.791,P=0.010）.Conclusion CDCs is suggested to be a promising cell source to repair acute myocardial infarction through inhibiting apoptosis and reduce proinflam-matory cytokine expression.

关 键 词：心肌梗死 缺血再灌注 心肌球源性干细胞 

分 类 号：R542.22[医药卫生—心血管疾病]