【摘要】 目的 探讨仙茅苷对心肌缺血再灌注(I/R)大鼠心肌损伤的改善作用及对微小RNA(miR)-155/Janus蛋白酪氨酸激酶2/信号转导及转录激活蛋白3(JAK2/STAT3)信号通路的调节作用。方法 将60只大鼠随机分为假手术组、模型组、仙茅苷组、miR-155过表达组和miR-155过表达+仙茅苷组。除假手术组外，其余组大鼠采用冠状动脉左前降支结扎法建立心肌I/R模型，仙茅苷组和miR-155过表达+仙茅苷组大鼠于建模前6 d腹腔注射仙茅苷50 mg/kg, 1次/d; miR-155过表达组和miR-155过表达+仙茅苷组大鼠于建模前在左心室上取3个位点注射miR-155 mimic。再灌注24 h后超声心动图检测心功能，TTC染色检测心肌梗死面积，实时荧光定量PCR(qRT-PCR)检测心肌组织中miR-155表达水平，苏木精-伊红(HE)染色观察心肌损伤病理表现，ELISA检测血清中肌酸激酶同工酶MB(CK-MB)、心肌肌钙蛋白T(cTnT)和乳酸脱氢酶(LDH)水平，蛋白质免疫印迹法检测心肌组织中p-JAK2和p-STAT3蛋白相对表达量。结果 与模型组比较，仙茅苷组心肌组织miR-155水平降低，心肌梗死面积减小，左室射血分数(LVEF)和左室缩短分数(LVFS)升高，左室舒张末期内径(LVESD)和左室收缩末期内径(LVEDD)减小，血清中CK-MB、cTnT、LDH水平下降，心肌组织中p-JAK2和p-STAT3蛋白相对表达量升高，而miR-155过表达组以上各指标变化趋势相反(均P<0.05);与miR-155过表达+仙茅苷组比较，miR-155过表达组miR-155水平升高，心肌梗死面积增大，LVEF和LVFS降低，LVESD和LVEDD增大，血清中CK-MB、cTnT、LDH水平上升，p-JAK2和p-STAT3蛋白相对表达量降低，而仙茅苷组以上各指标变化呈相反趋势(均P<0.05)。结论 仙茅苷可减轻大鼠心肌I/R损伤，改善心功能，其可能通过抑制miR-155表达从而上调JAK2/STAT3信号通路发挥作用。更多还原

【Abstract】 Objective To investigate the ameliorative effects of curculigoside on myocardial ischemia/reperfusion(I/R)injury in rats and the regulation of microRNA(miR-155)/Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway.Methods Sixty rats were randomly divided into sham operation group, model group, curculigoside group, miR-155 overexpression group and miR-155 overexpression + curculigoside group.Except for sham operation group, I/R models were established in other groups through ligation of left anterior descending coronary artery.Six days before modeling, the rats in the curculigoside group and the miR-155 overexpression + curculigoside group were introperitoneally injected with curculigoside(dose 50 mg/kg)once a day.The rats in the miR-155 overexpression group and the miR-155 overexpression + curculigoside group were injected with miR-155 mimic at 3 sites in the left ventricle 2 h before modeling.Then 24 h after reperfusion, echocardiography was used to detect cardiac function, TTC staining was used to detect myocardial infarction area, qRT-PCR was used to detect mir-155 expression level, and HE staining was used to observe myocardial pathological injury.The activities of creatine kinase isoenzyme MB(CK-MB),cardiac troponin T(cTnT)and lactate dehydrogenase(LDH)in serum were detected by ELISA,and the relative protein expression levels of p-JAK2 and p-STAT3 were detected by Western blotting.Results Compared with the model group, the miR-155 level was decreased, the myocardial infarction area was decreased, LVEF and LVFS were increased, LVESD and LVEDD were decreased, serum levels of CK-MB,cTnT and LDH were decreased and the relative protein expression levels of p-JAK2 and p-STAT3 were increased in curculigoside group, while the changes of above indexes showed an opposite trend in miR-155 overexpression group(P<0.05).Compared with miR-155 overexpression + curculigoside group, miR-155 level was increased, myocardial infarction size was increased, LVEF and LVFS were decreased, LVESD and LVEDD were increased, serum levels of CK-MB,cTnT and LDH were increased and relative protein expressions of p-JAK2 and p-STAT3 were decreased in miR-155 overexpression group.The changes of above indexes showed an opposite trend in curculigoside group(P<0.05).Conclusion Curculigoside can alleviate myocardial injury and improve cardiac function in I/R rats, which may play a role by inhibiting mir-155 expression and up-regulating JAK2/STAT3 signaling pathway.更多还原