乳酸和依达拉奉联用后适应通过p38／应激活化蛋白激酶途径减轻心肌细胞凋亡的研究  

Postconditioning of lactic acid and edaravone reduces apoptosis of myocardiocytes through the p38/JNK pathway

作　　者：张国明[1] 王禹[2] 李晓燕[1] 许琳[1] 苏绍萍[3] 孙媛媛[4] 刘丽凤[2] 沈红[1] 王晓菲[5] 

机构地区：[1]济南军区总医院心内科,250031 [2]解放军总医院老年心血管病研究所 [3]解放军总医院门诊部 [4]济南军区总医院超声科,250031 [5]济南军区联勤部门诊部

出　　处：《中华老年心脑血管病杂志》2013年第7期753-757,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(30740080);济南军区总医院院长青年基金(2011Q08)

摘　　要：目的探讨乳酸和低剂量依达拉奉能否模拟后适应通过p38/应激活化蛋白激酶(JNK)途径减轻心肌细胞凋亡。方法 108只雄性老年大鼠随机分为假手术组、缺血再灌注组(I/R组)、后适应组、乳酸组、低剂量依达拉奉组(Eda组)、乳酸+Eda组,每组18只。建立急性心肌梗死再灌注模型,测定再灌注10min后右心房血浆pH值,不同时间点处死大鼠,分别测定磷酸化p38/JNK、TNF-α、Caspase-8的表达以及心肌细胞凋亡。结果与I/R组比较,乳酸+Eda组血浆pH值、超氧化物歧化酶、细胞凋亡指数、磷酸化p38、磷酸化JNK、TNF-α、Caspase-8明显降低,差异有统计学意义(P<0.05),丙二醛明显升高,差异有统计学意义(P<0.05);与后适应组比较,乳酸+Eda组上述各项指标差异无统计学意义(P>0.05)。结论联合注射乳酸和低剂量依达拉奉可较好模拟机械后适应,通过p38/JNK途径减轻心肌细胞凋亡。Objective To study whether postconditioning of lactic acid and low edaravone dose re- duces apoptosis of myocardiocytes through the p38/JNK pathway. Methods One hundred and eight male elderly rats were randomly divided into sham operation group, reperfusion/injury group, postconditioning group, lactic acid group, low edaravone dose group, and lactic acid ＋ low edaravone dose group （18 in each group）. A rat acute myocardial infarction/reperfusion model was established. Ten minutes after reperfusion,the pH in right atrium was measured. The rats were killed at different time points and expressions of phosphorylated p38/JNK, TNF-α, caspase-8 and apoptosis of myocardiocytes were detected. Results The serum pH and superoxide dismutase lev- els,the apoptotic index, the expression levels of phosphorylated p38/JNK, TNF-α and caspase-8 were significantly lower whereas the serum MDA level was significantly higher in the lactic acid＋ low edaravone dose group than in the reperfusion/injury group （P〈0.05）. However,no signifi- cant difference was found in the above parameters between the postconditioning group and the lac- tic acid＋ low edaravone dose group （P〉0.05）. Conclusion Postconditioning of lactic acid in combination with low edaravone dose can reduce the apoptosis of myocardiocytes through the p38/JNK pathway.

关 键 词：乳酸 肌细胞 心脏 细胞凋亡 丙二醛 心肌再灌注 依达拉奉 

分 类 号：R542.22[医药卫生—心血管疾病]