雌二醇对大鼠心肌缺血/再灌注损伤的干预作用及其机制*

doi:10.12047/j.cjap.6362.2022.116

中国应用生理学杂志 ›› 2022, Vol. 38 ›› Issue (6): 638-643.doi: 10.12047/j.cjap.6362.2022.116

雌二醇对大鼠心肌缺血/再灌注损伤的干预作用及其机制^*

冯静茹¹, 张海洋², 史贺⁴, 王腾飞³, 王紫监², 程光慧², 毕胜利^1△

1.河北北方学院附属第二医院妇科,
2.河北北方学院附属第二医院心内科,
3.河北北方学院附属第二医院检验科, 张家口 075100;
4.石家庄市第四医院药剂科, 河北石家庄 050011

收稿日期:2022-10-08 修回日期:2022-11-24 出版日期:2022-11-28 发布日期:2023-06-12
通讯作者: ^△Tel: 13932348449; E-mail: 312339099@qq.com
基金资助:
^*河北省卫健委2020年医学科学研究课题计划(20200494)

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

FENG Jing-ru¹, ZHANG Hai-yang², SHI He⁴, WANG Teng-fei³, WANG Zi-jian², CHENG Guang-hui², BI Sheng-li^1△

1. Department of Gynecology, the Second Affiliated Hospital of Hebei North University, Zhangjiakou 075100;
2. Department of Cardiology, the Second Affiliated Hospital of Hebei North University, Zhangjiakou 075100;
3. Clinical Laboratory, the Second Affiliated Hospital of Hebei North University, Zhangjiakou 075100, China;
4. Department of Pharmacology, the Fourth Hospital of Shijiazhuang, Shijiazhuang 050011

Received:2022-10-08 Revised:2022-11-24 Online:2022-11-28 Published:2023-06-12

摘要/Abstract

摘要： 目的: 研究雌二醇(E2)通过雌激素受体β(ERβ)介导细胞外调节蛋白激酶(ERK)通路激活减轻心肌缺血/再灌注(I/R)损伤的作用及机制。方法: 84只成年雌性SD大鼠进行去卵巢手术并随机分为:对照组、NC-siRNA腺相关病毒(AAV)组进行假手术,I/R组、E2+I/R组、NC-siRNA AAV+I/R组、NC-siRNA AAV+E2+I/R组、ERβ-siRNA AAV+E2+I/R组。采用冠状动脉左前降支结扎的方法制备心肌I/R损伤模型,E2+I/R组、NC-siRNA AAV+E2+I/R组、ERβ-siRNA AAV+E2+I/R组造模前给予E2灌胃、连续60 d,NC-siRNA AAV+I/R组、NC-siRNA AAV+E2+I/R组、ERβ-siRNA AAV+E2+I/R组造模前24 h给予相应AAV尾静脉注射。再灌注120 min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,心肌中ERβ、p-ERK表达水平及肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、丙二醛(MDA)、总抗氧化力(T-AOC)的含量。结果: I/R组的血清LDH、CK、CK-MB含量、心肌梗死面积及心肌中TNF-α、IL-1β、MDA的含量均高于对照组,心肌中ERβ、p-ERK的表达水平及T-AOC的含量均低于对照组(P＜0.05);E2+I/R组的血清LDH、CK、CK-MB含量、心肌梗死面积及心肌中TNF-α、IL-1β、MDA的含量均低于I/R组,心肌中ERβ、p-ERK的表达水平及T-AOC的含量均高于I/R组(P＜0.05);尾静脉注射ERβ-siRNA AAV敲低ERβ的表达后,ERβ-siRNA AAV+E2+I/R组的血清LDH、CK、CK-MB含量、心肌梗死面积及心肌中TNF-α、IL-1β、MDA的含量均高于NC-siRNA AAV+E2+I/R组,心肌中ERβ、p-ERK的表达水平及T-AOC的含量均低于NC-siRNA AAV+E2+I/R组(P＜0.05)。结论: 雌二醇对去卵巢大鼠心肌I/R损伤具有保护作用,该作用与促进ERβ介导ERK通路激活、减轻炎症反应及氧化应激反应有关。

关键词: 心肌缺血/再灌注, 雌二醇, 雌激素受体β, 细胞外调节蛋白激酶, 炎症反应, 氧化应激, 大鼠

Abstract: Objective: 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. Methods: 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. Results: 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 (P＜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(P＜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(P＜0.05). Conclusion: 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.

Key words: myocardial ischemia/reperfusion, estradiol, estrogen receptor β, extracellular regulated protein kinase, inflammatory response, oxidative stress response, rats

中图分类号:

R542

冯静茹, 张海洋, 史贺, 王腾飞, 王紫监, 程光慧, 毕胜利. 雌二醇对大鼠心肌缺血/再灌注损伤的干预作用及其机制^*[J]. 中国应用生理学杂志, 2022, 38(6): 638-643.

FENG Jing-ru, ZHANG Hai-yang, SHI He, WANG Teng-fei, WANG Zi-jian, CHENG Guang-hui, BI Sheng-li. Intervention effects of estradiol on myocardial ischemia- reperfusion injury of rat and its mechanisms[J]. CJAP, 2022, 38(6): 638-643.

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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

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