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中华养生保健 ›› 2023, Vol. 41 ›› Issue (24): 14-17.

• 论著 • 上一篇    下一篇

内源性抗氧化剂金属硫蛋白对慢性间歇性乏氧引起的心肌损害的保护性作用及机制研究

王鹤儒1, 尹霞2, 夏彬凤2, 郑庆霜3, 崔明月2   

  1. 1.浙江大学医学院附属第一医院心血管超声中心,浙江 杭州,310000;
    2.吉林大学白求恩第一医院心血管内科,吉林 长春,130000;
    3.吉林大学中日联谊医院老年病科,吉林 长春,130000
  • 出版日期:2023-12-16 发布日期:2023-12-07
  • 作者简介:王鹤儒(1993—),女,汉族,籍贯:浙江省杭州市,硕士研究生,医师,研究方向:心肌痛。
  • 基金资助:
    吉林省自然基金学科布局项目(省联合基金白求恩医学专项)(20200201609JC)

Protective Effect and Mechanism of Endogenous Antioxidant Metallothionein on Myocardial Damage Caused by Chronic Intermittent Hypoxia

WANG He-ru1, YIN Xia2, XIA Bin-feng2, ZHENG Qing-shuang3, CUI Ming-yue2   

  1. 1. Cardiovascular Ultra Sound Center of the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou Zhejiang 310000, China;
    2. Department of Cardiovascular Medicine, Bethune First Hospital of Jilin University, Changchun Jilin 130000, China;
    3. Geriatric Department of the Jilin University Sino Japanese Friendship Hospital, Changchun Jilin 130000, China
  • Online:2023-12-16 Published:2023-12-07

摘要: 目的 明确慢性间歇性乏氧(CIH)条件下,锌及萝卜硫素(SFN)是否可通过上调金属硫蛋白(MT)在心肌中的表达对CIH所致的心肌损伤发挥保护性作用并探讨其机制。方法 8周龄雄性昆明小鼠,随机分为对照组、CIH组、CIH+N.S组、锌防护组、SFN防护组,除对照组外全部暴露于CIH环境下构建CIH引起的心肌损害模型,同时防护组及生理盐水组分别给予硫酸锌(5 mg/kg)、SFN(0.5 mg/kg)、同等体积的0.9%氯化钠溶液。8周后利用超声心动图、天狼猩红染色、免疫组化及免疫印迹等方法检测小鼠心脏结构及功能,心肌组织中胶原纤维、MT、核因子E2相关因子 2(Nrf2)及蛋白激酶B(Akt)等细胞因子的表达等。结果 CIH组与对照组相比,小鼠心室扩张,心功能降低,心肌纤维化程度增加,差异有统计学意义(P<0.05);硫酸锌及SFN防护组与CIH组相比,小鼠心室扩张、心功能降低、心肌纤维化程度均减轻,差异有统计学意义(P<0.05);硫酸锌及SFN防护组与CIH组相比,小鼠心肌组织中MT、Nrf2及Akt2的表达增高,差异有统计学意义(P<0.05)。结论 CIH可导致小鼠心肌损伤,锌及SFN对CIH所致的心肌损伤有保护性作用,这可能与上调MT、Nrf2及Akt2的表达有关。

关键词: 慢性间歇性乏氧, 心肌损伤, 金属硫蛋白, 核因子E2相关因子2, 硫酸锌, 萝卜硫素

Abstract: Objective To determine whether zinc and sulforaphane (SFN) can play a protective role in myocardial injury induced by chronic intermittent hypoxia (CIH) through up-regulating the expression of metallothionein (MT) in myocardium,and to explore its mechanism. Methods 8-week-old male Kunming mice were randomly divided into control group, CIH group, CIH+N. S group, zinc protection group and SFN protection group. All of them were exposed to CIH environment except the control group to construct myocardial damage model induced by CIH. At the same time, the protection group and the normal saline group were injected with zinc sulfate (5 mg/kg), SFN (0.5 mg/kg) and the same volume of normal saline respectively. After 8 weeks, echocardiography, Sirius scarlet staining, immunohistochemistry and western blot were used to detect the cardiac structure and function of mice, the expression of collagen fibers, MT, nuclear factor E2 related factor 2 (Nrf2) and protein kinase B (Akt) in myocardial tissue. Results Compared with control group, CIH group showed ventricular dilation, decreased cardiac function and increased degree of myocardial fibrosis, the difference was statistically significant (P<0.05); Compared with CIH group, the dilation of heart, cardiac insufficiency and myocardial fibrosis of mice in zinc sulfate and SFN protection group were reduced, and the difference was statistically significant (P<0.05); Compared with CIH group, the expressions of MT, Nrf2 and Akt2 in myocardium of mice were increased in zinc sulfate and SFN protection group , and the differences were statistically significant (P<0.05). Conclusion CIH can cause myocardial injury in mice, and zinc and SFN have protective effects on CIH-induced myocardial injury, which may be related to the up-regulation of MT, Nrf2 and Akt2 expression.

Key words: chronic intermittent hypoxia, myocardial injury, metallothionein, nuclear factor E2 related factor 2, zinc sulfate, sulforaphane

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