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白藜芦醇通过调控Notch信号通路对大鼠肝脏缺血/再灌注损伤时心脏损伤的预防机制研究

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

作者信息

Lu Yan-Zhen, Wang Jia, Song Juan, Li Bao-Hong, Guo Ya-Ling, Wang Dong, Zhang Cui-Ying

机构信息

Department of Pathophysiology, Changzhi Medical College, Changzhi 046000, China.

Department of Immunology, Changzhi Medical College, Changzhi 046000, China.

出版信息

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2016 Apr 8;32(4):351-355. doi: 10.13459/j.cnki.cjap.2016.04.017.

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(<0.01), the activity of SOD in myocardum was decreased and contents of MDA in myocardum was enhanced (<0.01). Compared with HIR group, the left ventricular functions were significantly en-hanced in Res group (<0.01). The above mentioned parameters in the serum in the Res group were evidently improved (<0.01), meanwhile the expression of NICD and Notchl were significantly enhanced whereas the expression of TNF-α was obviously decreased.

CONCLUSIONS

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 Notch signaling pathway.

摘要

目的

研究Notch1信号通路在肝缺血/再灌注损伤后白藜芦醇预处理心肌保护作用中的作用。

方法

将36只健康雄性SD大鼠随机分为3组:假手术对照组(SC组)、肝缺血/再灌注(HIR)组和白藜芦醇预处理(Res)组,每组12只。各组肝缺血40分钟再灌注2小时后(SC组放置相同时间),测量左心室功能,包括左心室压力(LVP)、左心室收缩压(LVSP)及其导数(±dp/dt);检测血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、肿瘤坏死因子α(TNF-α)和白细胞介素-6(IL-6)的活性。测定心肌超氧化物歧化酶(SOD)活性和心肌丙二醛(MDA)含量;用蛋白质印迹法检测Notch细胞内结构域(NICD)表达;用实时PCR检测Notch1和TNF-α的mRNA水平。

结果

与SC组相比,HIR组左心室功能明显降低。随着NICD和Notch1表达降低,血清中CK-MB、LDH、TNF-α和IL-6活性明显升高(P<0.01),心肌SOD活性降低,心肌MDA含量升高(P<0.01)。与HIR组相比,Res组左心室功能明显增强(P<0.01)。Res组血清中上述参数明显改善(P<0.01),同时NICD和Notch1表达明显增强,而TNF-α表达明显降低。

结论

研究结果表明,白藜芦醇对肝缺血/再灌注期间的心肌损伤具有保护作用,其机制可能与抗炎和抗氧化应激Notch信号通路有关。

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