NOTCH1信号通路介导白藜芦醇抗肝缺血/再灌注所致大鼠心脏损伤保护作用的机制研究

目的：观察Notch1信号通路在肝缺血/再灌注损伤时对心脏损伤的保护作用并探讨其相关的机制。方法：36只健康雄性SD大鼠随机分为3组，假手术组（SC组）、肝缺血/再灌注组（HIR组）、白藜芦醇预处理组（Res处理组），每组12只。各组均与肝脏缺血40 min再灌注2 h（SC组旷置相等时间）后，记录左室血流动力学变化，测定血清肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）、肿瘤坏死因子（TNF-α）和白细胞介素-6（IL-6）浓度，取心肌组织测定SOD活力及MDA含量，Western blot检测心肌组织反应Notch通路活化标志的NICD表达，以RT-PCR法从转录水平检测Notch1和TNF-α的表达水平。结果：与SC比较，HIR组左室收缩及舒张功能均显著降低（P<0.01），血清CK、LDH活力，TNF-α和IL-6浓度明显升高（P<0.01），心肌MDA含量明显升高而SOD活力明显降低（P<0.01），且Notch1表达下降，TNF-α表达增加；与I/R组相比，Res处理组左室舒缩功能明显升高，血清CK、LDH活力及TNF-α、IL-6浓度明显降低，同时心肌SOD活力明显升高而MDA含量明显降低，Notch1表达上升TNF-α表达降低。结论：白藜芦醇对肝缺血/再灌注大鼠心脏具有保护作用，其机制可能与Notch1信号通路的激活进而调节炎症反应及氧化应激有关。

A study on preventive mechanisms of resveratrol on injuried heart during hepatic ischemia/reperfusion injury in rats by regulating Notch signaling pathway

Objective:To study the role of Notch1 signaling pathway in the myocardial protective effects of resveratrol pro-treatment after hepatic ischemia/reperfusion injury. Methods:Thirty-six healthy male SD rats were randomly divided into 3 groups:sham control (SC) group, hepatic ischemic/reperfusion (HIR) group, and pro-treatment resveratrol (Res) group,12 rats in each group. After each group with hepatic ischemia 40 min reperfusion 2 h (SC group placing equal time), the left ventricular function including left ventricular pressure (LVP), left ventricular systolic pressure (LVSP) and its derivate (±dp/dt) was measured; the serum activities of creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH) and tumor necrosis factorα(TNF-α) and interleukin-6(IL-6) were detected. The activity of myocardial su-peroxide dismutase(SOD) and contents of myocardial malonaldehyde (MDA) were determined; Notch intracellular domain (NICD) expressions were detected with Western blot; the mRNA levels of Notch1 and TNF-αwere detected by real-time PCR. Results:Compared with SC group, the left ventricular functions in the HIR group were significantly decreased. With decreasing the expression of NICD and Notchl, the activities of CK-MB, LDH, TNF-αand IL-6 in the serum were evidently increased(P<0.01), the activity of SOD in myocardum was decreased and contents of MDA in myocardum was enhanced (P<0.01). Compared with HIR group, the left ventricular functions were significantly en-hanced in Res group (P<0.01). The above mentioned parameters in the serum in the Res group were evidently improved (P<0.01), meanwhile the expression of NICD and Notchl were significantly enhanced whereas the expression of TNF-α was obviously decreased. Conclusion:The findings indicate that resveratrol has protective effect on myocardial injury during the hepatic ischemia/reperfusion, and its mecha-nisms may be related to anti-inflammation and anti-oxidative stress via Notch signaling pathway.