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

doi:10.13459/j.cnki.cjap.2016.04.017

中国应用生理学杂志 ›› 2016, Vol. 32 ›› Issue (4): 351-355.doi: 10.13459/j.cnki.cjap.2016.04.017

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

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

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. 长治医学院教改班 2011 级、2013 级, 山西长治 046000;
4. 长治医学院生理学教研室, 山西长治 046000

收稿日期:2016-01-21 修回日期:2016-04-08 出版日期:2016-07-28 发布日期:2018-06-20
通讯作者: 张翠英,Tel:0355-3151440;E-mail:zhangcy157@sohu.com E-mail:zhangcy157@sohu.com
基金资助:
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）

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

LU Yan-zhen¹, WANG Jia², SONG Juan¹, LI Bao-hong¹, GUO Ya-ling³, WANG Dong³, ZHANG Cui-ying⁴

1. Department of Pathophysiology, Changzhi Medical College, Changzhi 046000, China;
2. Department of Immunology, Changzhi Medical College, Changzhi 046000, China;
3. Department of Reform of Education and Teaching Class of 2011 and 2013, Changzhi Medical College, Changzhi 046000, China;
4. Department of Physiology, Changzhi Medical College, Changzhi 046000, China

Received:2016-01-21 Revised:2016-04-08 Online:2016-07-28 Published:2018-06-20
Supported by:
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/Abstract

摘要： 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。

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

Abstract: 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.

Key words: hepatic ischemia/reperfusion injury, resveratrol, Notch signaling pathway, inflammation, oxidative stress

卢彦珍, 王佳, 宋娟, 李宝红, 郭雅玲, 王东, 张翠英. 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[J]. 中国应用生理学杂志, 2016, 32(4): 351-355.

LU Yan-zhen, WANG Jia, SONG Juan, LI Bao-hong, GUO Ya-ling, WANG Dong, ZHANG Cui-ying. A study on preventive mechanisms of resveratrol on injuried heart during hepatic ischemia/reperfusion injury in rats by regulating Notch signaling pathway[J]. CJAP, 2016, 32(4): 351-355.

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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

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