Ginkgo biloba extract-761 protects myocardium by regulating Akt/Nrf2 signal pathway
Ginkgo biloba extract-761 protects myocardium by regulating Akt/Nrf2 signal pathway
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DOI：
10.2147/dddt.s191537
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发表时间：
2019-01-01
影响因子：
4.8
通讯作者：
Tao, Hai-long
中科院分区：
文献类型：
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作者：
Chen, Xiao-jie;Ren, Shu-min;Tao, Hai-long
目的：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：40只SD大鼠随机分为假手术组、I/R组和银杏叶提取物761(20，40 mg/kg)组。给药14d后建立MIRI模型。测量并比较两组心肌梗死面积和心肌组织学变化。同时检测血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDII)、肌钙蛋白T(TnT)、肿瘤坏死因子-α(TNF-α)、白介素6(IL-6)、白介素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)水平。免疫印迹法检测Caspase-3、Bax、Bel-2、HO-1、Nrf2、Akt、p-Akt和核蛋白Nrf2的表达。结果：EGb761组心肌梗死面积、CK-MB、LDH、TnT、TNF-α、IL-6和IL-1β水平明显低于缺血再灌注组。心肌组织中丙二醛含量低于I/R组，而超氧化物歧化酶和谷胱甘肽过氧化物酶活性高于I/R组。EGB 761组Caspase-3、Bax的表达明显低于I/R组，而Bcl2、p-Akt、HO-1及核蛋白Nrf2的表达明显高于I/R组。结论：EGb 761可能通过激活Akt/Nrf2通路，上调HO-1的表达，减轻氧化应激，抑制炎症反应，从而抑制心肌细胞的凋亡，从而保护心肌。
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 dehydrogenate: (LDII), troponin T (TnT), TNF-alpha, IL-6, IL-1 beta, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were evaluated. Western blot was used to detect the expression of Caspase-3, Bax, Bel-2, HO-1, Nrf2, Akt, p-Akt and nuclear protein Nrf2.Results: The levels of infarct size, CK-MB, LDH, TnT, TNF-alpha, IL-6 and IL-1 beta 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.