牛磺酸对缺血-再灌注大鼠血浆心肌肌钙蛋白T及心肌GRP78、Caspase-12表达的影响

摘要

Objective To explore the effects of taurine (Tau) on plasma cardiac troponin T (cTnT) levels and myocardial glucose-regulated protein 78 (GRP78) and caspase-12 expression in rats undergoing ischemia-reperfusion (I/R). Methods Fifty rats were randomly divided into five groups; sham operation group (sham group), I/R group, I/R+ Tau 100 mg · kg-1 (Tau 1 group), I/R+Tau 200 mg · kg-1 (Tau 2 group), I/R+ Tau 300 mg · kg-1 (Tau 3 group),with 10 rats in each group. Myocardial I/R injury was induced by left anterior descending artery (LAD) ligation for 1 hour and reperfusion for 24 hours. Tau was intraperitoneally injected 1 hour before LAD ligation. Rats in sham group underwent placement of suture without ligation. Plasma cTnT levels were measured by ELISA. Cardiomyocyte apoptosis was detected by TUNEL assay. The expression of GRP78 and caspase-12 was determined by RT-PCR and immunohistochemistry. Caspase-3 activity was examined by fluorospeclropholomelry. Results Compared with sham group, plasma cTnT levels, myocardial mRNA and protein expression of GRP78 and caspase-12, apoptosis index, and caspase-3 activity significantly increased in I/R group (all P<0.01). Compared with I/R group, cTnT levels, GRP78 and caspase-12 expression, apoptosis index, and caspase-3 activity obviously decreased in Tau 1, Tau 2 and Tau 3 groups (all P<0.05). Conclusion Tau can attenuate myocardial I/R injury through down-regulating the expression of myocardial GRP78 and caspase-12.%目的 探讨牛磺酸(taurine,Tau)对心肌缺血-再灌注损伤时血浆心肌肌钙蛋白T(cardiac troponin T,cTnT)及心肌葡萄糖调节蛋白78(glucose-regulated protein 78,GRP78)、胱天蛋白酶(Caspases)-12表达的影响及其意义.方法 将50只大鼠按随机数字表法分为5组:假手术组(对照组,Sham组)、缺血-再灌注组(I/R组)和Tau保护1组(Tau 1组)、Tau保护2组(Tau 2组)、Tau保护3组(Tau 3组),每组10只.采用结扎大鼠冠状动脉左前降支1 h,随后再灌注24 h以建立心肌缺血-再灌注损伤动物模型;Tau 1组、Tau 2组、Tau 3组分别在结扎冠状动脉前1 h腹腔注射Tau 100、200、300 mg·kg-1,余操作同I/R组;Sham组大鼠冠状动脉左前降支仅穿线,不结扎.采用酶联免疫法测定血浆cTnT水平,TUNEL法检测心肌细胞凋亡,RT-PCR法和免疫组织化学法分析心肌细胞GRP78、Caspase-12基因表达,荧光分析法测定Caspase-3活性.结果 与Sham组比较,I/R组大鼠血浆 cTnT 、心肌组织中GRP78、Caspase-12 mRNA和蛋白表达、细胞凋亡指数及Caspase-3活性均显著升高(均P＜0.01);与I/R组比较,Tau 1组、Tau 2组、Tau 3组大鼠血浆 cTnT 水平、心肌组织中GRP78 mRNA、Caspase-12 mRNA和蛋白表达、细胞凋亡指数及Caspase-3活性均呈显著降低(均P＜0.05).结论 Tau可显著减轻心肌缺血-再灌注损伤,其作用机制可能是Tau能下调缺血-再灌注心肌中GRP78 和 Caspase-12过表达.