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[雌二醇对大鼠心肌缺血再灌注损伤的干预作用及其机制]

[Intervention effects of estradiol on myocardial ischemia- reperfusion injury of rat and its mechanisms].

作者信息

Feng Jing-Ru, Zhang Hai-Yang, Shi He, Wang Teng-Fei, Wang Zi-Jian, Cheng Guang-Hui, Bi Sheng-Li

机构信息

Department of Gynecology, the Second Affiliated Hospital of Hebei North University, Zhangjiakou 075100.

Department of Cardiology, the Second Affiliated Hospital of Hebei North University, Zhangjiakou 075100.

出版信息

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2022 Nov;38(6):638-643. doi: 10.12047/j.cjap.6362.2022.116.

Abstract

To study the effects of estradiol (E2) on alleviating myocardial ischemia/reperfusion(I/R) injury through estrogen receptorβ(ERβ) mediated extracellular regulated protein kinases(ERK) pathway activation. Eighty-four adult female SD rats were ovariectomized and randomly divided into control group, NC siRNA adeno-associated virus (AAV) group received sham operation, the myocardial I/R injury model was prepared by ligation of the left anterior descending coronary artery in I/R group, E2+I/R group, NC siRNA AAV+I/R group, NC siRNA AAV+E2+I/R group and ERβ-siRNA AAV+E2+I/R group. E2+I/R group, NC siRNA AAV+E2+I/R group and ERβ-siRNA AAV+E2+I/R group were treated with E2 0.8 mg/kg by gavage for 60 days before modeling. NC siRNA AAV+I/R group, NC siRNA AAV+E2+I/R group, and ERβ-siRNA AAV+E2+I/R group were treated with AAV by caudal vein injection 24 h before modeling. After 120 min of reperfusion, the contents of serum lactate dehydrogenase (LDH), phosphocreatine kinase (CK), phosphocreatine kinase isoenzyme (CK-MB), myocardial infarction area and the expressions of ERβ, p-ERK, the contents of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1 β), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) in myocardium were measured. The contents of serum LDH, CK, CK-MB, myocardial infarction area and the contents of TNF-α, IL-1 β, MDA in myocardium of I/R group were higher than those of the control group, the expression levels of ERβ and p-ERK and the content of T-AOC were lower than those in the control group (<0.05). The contents of serum LDH, CK and CK-MB, myocardial infarction area and the contents of TNF-α, IL-1 β and MDA in myocardium of E2+I/R group were lower than those of the I/R group, the expression levels of ERβ and p-ERK and the content of T-AOC were higher than those of the I/R group(<0.05). After knockdown ERβ by caudal vein injection of ERβ-siRNA AAV, the contents of serum LDH, CK and CK-MB, myocardial infarction area and the contents of TNF-α, IL-1 β and MDA in myocardium of ERβ-siRNA AAV+E2+I/R group were higher than those of NC-siRNA AAV+E2+I/R, the expression levels of ERβ and p-ERK and the content of T-AOC were lower than those of NC-siRNA AAV+E2+I/R(<0.05). E2 has protective effects on myocardial I / R injury in ovariectomized rats, which are related to the promotion of ERβ mediating the activation of ERK pathway, reducing inflammatory and oxidative stress responses.

摘要

研究雌二醇(E2)通过雌激素受体β(ERβ)介导的细胞外调节蛋白激酶(ERK)通路激活来减轻心肌缺血/再灌注(I/R)损伤的作用。将84只成年雌性SD大鼠去卵巢后随机分为对照组、接受假手术的NC siRNA腺相关病毒(AAV)组、I/R组、E2+I/R组、NC siRNA AAV+I/R组、NC siRNA AAV+E2+I/R组和ERβ-siRNA AAV+E2+I/R组,I/R组通过结扎左冠状动脉前降支制备心肌I/R损伤模型。E2+I/R组、NC siRNA AAV+E2+I/R组和ERβ-siRNA AAV+E2+I/R组在建模前60天通过灌胃给予E2 0.8 mg/kg。NC siRNA AAV+I/R组、NC siRNA AAV+E2+I/R组和ERβ-siRNA AAV+E2+I/R组在建模前24小时通过尾静脉注射AAV。再灌注120分钟后,检测血清乳酸脱氢酶(LDH)、磷酸肌酸激酶(CK)、磷酸肌酸激酶同工酶(CK-MB)含量、心肌梗死面积以及心肌中ERβ、p-ERK的表达、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、丙二醛(MDA)含量和总抗氧化能力(T-AOC)。I/R组血清LDH、CK、CK-MB含量、心肌梗死面积以及心肌中TNF-α、IL-1β、MDA含量高于对照组,ERβ和p-ERK表达水平及T-AOC含量低于对照组(<0.05)。E2+I/R组血清LDH、CK和CK-MB含量、心肌梗死面积以及心肌中TNF-α、IL-1β和MDA含量低于I/R组,ERβ和p-ERK表达水平及T-AOC含量高于I/R组(<0.05)。通过尾静脉注射ERβ-siRNA AAV敲低ERβ后,ERβ-siRNA AAV+E2+I/R组血清LDH、CK和CK-MB含量、心肌梗死面积以及心肌中TNF-α、IL-1β和MDA含量高于NC-siRNA AAV+E2+I/R组,ERβ和p-ERK表达水平及T-AOC含量低于NC-siRNA AAV+E2+I/R组(<0.05)。E2对去卵巢大鼠心肌I/R损伤具有保护作用,这与促进ERβ介导的ERK通路激活、减轻炎症和氧化应激反应有关。

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