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  

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

作　　者：卢彦珍[1] 王佳[2] 宋娟[1] 李宝红[1] 郭雅玲[3] 王东[3] 张翠英[4] 

机构地区：[1]长治医学院病理生理学教研室,山西长治046000 [2]长治医学院免疫学教研室,山西长治046000 [3]长治医学院,山西长治046000 [4]长治医学院生理学教研室,山西长治046000

出　　处：《中国应用生理学杂志》2016年第4期351-355,共5页Chinese Journal of Applied Physiology

基　　金：山西省自然科学基金资助项目(2009011055);山西省2013年国家级大学生创新创业训练资助项目(2013083);长治医学院科技启动基金资助项目(QDZ201520)

摘　　要：目的:观察Notchl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Ⅱ-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。Objective： To study the role of Notchl 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 iscbemia 40 min reperfusion 2 h （SC group placing equal time）, the left ventricular function including left ventrictdar 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 factor α（TNF-α） and interleukin-6（IL-6） were detected. The activity of myocardial superoxide dismntase（SOD） and contents of myocardial malonaldehyde （MDA） were determined; Notch intracellular domain （NICD） expressions were detected with Western blot; the mRNA levels of Notchl and TNF-α were 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 Notch1, the activities of CK-MB, LDH, TNF-α and 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 enhanced 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 mechanisms may be related to anti-inflanmaation and

关 键 词：肝缺血/再灌注损伤 白藜芦醇 NOTCH信号通路 炎症反应 氧化应激 

分 类 号：R541[医药卫生—心血管疾病]