促心肌素C-末端肽对再灌注损伤大鼠心肌细胞凋亡的影响

目的观察促心肌素（CT-1）C-末端肽在缺血再灌注损伤前后进行干预对大鼠心肌细胞凋亡的影响。方法制备心肌缺血再灌注损伤（MI/R）模型,27只SD大鼠随机分为正常组（N,n=5）、再灌注损伤模型组（D,n=6）、MI/R后CT-1干预组（T,n=8）和MI/R前CT-1干预组（O,n=8）。检测各组血清肌酸激酶（CK）活性和丙二醛（MDA）浓度;并取缺血区及其周围心脏组织计算心肌细胞凋亡指数（AI）。结果 MI/R后,模型组SD大鼠的平均存活时间为（93.17±24.7）min,在MI/R前的CT-1干预组为（87.88±18.3）min,MI/R后的CT-1干预组为（155.5±80.13）min,明显长于模型组和MI/R前干预组（q值分别为3.171、3.716,P〈0.01）;模型组SD大鼠的血清CK、MDA浓度升高,梗死区周围的AI也升高（N vs D,q值分别为14.391、11.015、21.668,P〈0.01）;MI/R后CT-1干预组的大鼠,血清CK、MDA浓度及AI均有所降低（T vs D,q值分别为10.649、6.167、16.493,P〈0.01）,但仍高于正常组（q值分别为5.197、5.782、7.391,P〈0.01）;CT-1前干预组的动物,血清CK、MDA浓度明显高于模型组（q值分别为6.147、10.551,P〈0.01）,AI高于正常组（q=24.609,P〈0.01）,但与模型组比较无明显差异（q=1.683,P〉0.05）;心肌细胞的凋亡情况与心肌的损伤及氧化损伤程度,有明显的相关性（r值分别为0.9245、0.8679,P〈0.01）。结论 CT-1 C-末端多肽再灌注早期短期使用能减轻心肌组织损伤及氧化损伤,以及心肌细胞凋亡的程度,使动物存活时间延长;但腹腔注射CT-1 C-末端多肽较长时间后,大鼠对MI/R的耐受力降低,组织损伤及氧化损伤的程度明显加重,且梗死周边区有相当的心肌细胞发生凋亡,动物的存活时间也较短。

Effects of cardiotrophin-1 C-terminal peptides on cardiomyocyte apoptosis in SD rats following myocardial ischemia-reperfusion injury

Aim To study the effects of cardiotrophin-1（CT-1） C-terminal peptides in myocardial ischemia-reperfusion injury（MI/R） before and after the intervention on myocardial cell apoptosis in SD rats.Methods The ischemia reperfusion heart models in 27 SD rats were established and divided into four groups（group N,D,T and O）：Normal group（N,n=5）;Disease group（D,n=6）;Reperfusion after 30 minutes of MI,post-MI/R CT-1 intervention group（T,n=8）,intraperitoneal injection of CT-1 C-terminal peptide（100μg/kg） at same time of reperfusion after 30 minutes of MI,pre-MI/R CT-1 intervention group（O,n=8）,MI/R was performed after injection of CT-1 for 7days.The concentrations of CK and MDA were measured at the same time.The apoptosis of myocardial cells in ischemic heart tissue were observed by the end-labeling TUNEL assay and the cardiac myocyte apoptotic index（AI） were calculated.Results After MI/R,the average survival time of D group was 93.17 ± 24.7 minutes,that of T group was 87.88 ± 18.3 minutes.The average survival time of O group was 155.5 ± 80.13 minutes,significantly longer than that of D and T groups（P0.01）;The serum CK activity and MDA content and AI around infarct area were increased significantly in D group（P0.01）,and that reduced significantly in the T group（P0.01）.but still higher than that of normal group（P0.01）;The serum CK activity and MDA content were much higher in O group than that of D group,and their apoptosis index（AI） were higher than that of normal group（P0.01）,but without significant difference compared with the D group（P0.05）.There were significant correlations between the myocardial apoptosis with myocardial injury and the extent of oxidative damage（P0.01）.Conclusion Short-term use of CT-1C-terminal peptide early in reperfusion can reduce myocardial tissue injury,oxidative damage,and the extent of cardiomyocyte apoptosis,as well as prolong animal survival time.