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提取物-761通过调节Akt/Nrf2信号通路来保护心肌。

extract-761 protects myocardium by regulating Akt/Nrf2 signal pathway.

作者信息

Chen Xiao-Jie, Ren Shu-Min, Dong Jian-Zeng, Qiu Chun-Guang, Chen Ying-Wei, Tao Hai-Long

机构信息

Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China,

Department of Genetics and Prenatal Diagnosis, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

出版信息

Drug Des Devel Ther. 2019 Feb 13;13:647-655. doi: 10.2147/DDDT.S191537. eCollection 2019.

Abstract

OBJECTIVE

The aim of this study was to investigate the protective effect and mechanism of Ginkgo biloba extract-761 (EGb 761) in the rat with myocardial ischemia-reperfusion injury (MIRI).

MATERIALS AND METHODS

Forty Sprague Dawley rats were randomly divided into following four groups: sham group, I/R group and EGb 761 groups (20 and 40 mg/kg). MIRI model was established after 14 days of administration. The myocardial infarct size and myocardial histology were measured and compared. Meanwhile, the levels of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin T (TnT), TNF-α, IL-6, IL-1β, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were evaluated. Western blot was used to detect the expression of Caspase-3, Bax, Bcl-2, HO-1, Nrf2, Akt, p-Akt and nuclear protein Nrf2.

RESULTS

The levels of infarct size, CK-MB, LDH, TnT, TNF-α, IL-6 and IL-1β in the EGb 761 groups were significantly lower than those in the ischemia/reperfusion (I/R) group. The content of MDA was lower in the myocardium, whereas the activities of SOD and GSH-Px were higher than those in the I/R group. The expressions of Caspase-3 and Bax in the EGb 761 groups were significantly lower than those in the I/R group, whereas the expressions of Bcl-2, p-Akt and HO-1 and nuclear protein Nrf2 in the EGb 761 groups were higher than those in the I/R group.

CONCLUSION

EGb 761 might inhibit the apoptosis of myocardial cells and protect the myocardium by activating the Akt/Nrf2 pathway, increasing the expression of HO-1, decreasing oxidative stress and repressing inflammatory reaction.

摘要

目的

本研究旨在探讨银杏叶提取物761(EGb 761)对大鼠心肌缺血再灌注损伤(MIRI)的保护作用及其机制。

材料与方法

将40只Sprague Dawley大鼠随机分为以下四组:假手术组、缺血/再灌注(I/R)组和EGb 761组(20 mg/kg和40 mg/kg)。给药14天后建立MIRI模型。测量并比较心肌梗死面积和心肌组织学。同时,评估肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、肌钙蛋白T(TnT)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-Px)的水平。采用蛋白质免疫印迹法检测半胱天冬酶-3(Caspase-3)、Bax、Bcl-2、血红素加氧酶-1(HO-1)、核因子E2相关因子2(Nrf2)、蛋白激酶B(Akt)、磷酸化Akt(p-Akt)及核蛋白Nrf2的表达。

结果

EGb 761组的梗死面积、CK-MB、LDH、TnT、TNF-α、IL-6和IL-1β水平显著低于缺血/再灌注(I/R)组。心肌中MDA含量降低,而SOD和GSH-Px活性高于I/R组。EGb 761组中Caspase-3和Bax的表达显著低于I/R组,而EGb 761组中Bcl-2、p-Akt、HO-1及核蛋白Nrf2的表达高于I/R组。

结论

EGb 761可能通过激活Akt/Nrf2通路、增加HO-1表达、减轻氧化应激和抑制炎症反应来抑制心肌细胞凋亡并保护心肌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb8d/6387611/2607bcafabd2/dddt-13-647Fig1.jpg

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