抑制JAK/STAT通路对培养乳鼠心肌细胞模拟缺血/再灌注损伤的作用

The cardioprotective effect of the inhibitor of JAK/STAT on simulating ischemia-reperfusion injury in cultured immature rat cardiacmyocytes

目的研究抑制Janus激酶/信号转导和转录激活子(JAK/STAT)通路对乳鼠心肌细胞缺血再灌注损伤的保护作用。方法采用体外培养的新生大鼠心肌细胞造成缺血再灌注(I/R)模型,随机分为正常对照组,缺血再灌注组,JAK抑制剂-AG490治疗组,STAT抑制剂-RMP治疗组。采用MTT法检测心肌细胞活性,检测以上不同条件下细胞上清液中的乳酸脱氢酶(LDH)、丙二醛(MDA)、超氧化物歧化酶(SOD)含量,并检测各组细胞的凋亡率。结果与正常对照组相比,缺血再灌组心肌细胞成活率明显降低(P<0.01),细胞上清液中LDH、MDA含量明显升高(P<0.01),SOD活力则显著降低(P<0.01),缺血再灌组凋亡率升高明显(P<0.01)。AG490及RMP处理后,心肌细胞成活率明显升高(P<0.01),LDH、MDA显著低于缺血再灌组(P<0.01),SOD则高于缺血再灌组(P<0.01)。结论抑制JAK/STAT通路有助于减轻缺血再灌注所致心肌损伤。

Objective To investigate the cardioprotective effects of the irthibitor of JAK/STAT pathway on ischemia-reperfusion injury in cultured immature rat cardiacmyocytes. Methods The cultured immature rat cardiacmyocytes were randomly divided into normal control group, iscbemia-reperfusion group, AG490 treatment group and RMP treatment group. The cell viability was measured by MTr method. The contents of lactate dehydrogenase （LDH） and malondialdehyde （MDA）, the superoxide dismutase （SOD） activity and the rate of cell apoptosis were detected. Results Compared with the normal group, the cell viability decreased significantly, the contents of LDH and MDA in the supernatant of the cells increased significantly, the SOD activity decreased and the rate of apoptosis of cells＇increased significantly in ischemia-reperfusion group （all P 〈0. 01 ）. With the treatment of AG490 or RMP, the survival rate of the cells was increased significantly, and the contents of LDH and MDA were decreased significantly （ all P 〈 0. 01 ）. Conclusion Early treatment with inhibitors to JAK/STAT pathway may be benefit for the attenuation of myocardial injury induced by ischemia-reperfusion.