基于氧化应激探讨硫化氢改善阻塞性睡眠呼吸暂停诱发房颤的作用机制

doi:10.6040/j.issn.1671-7554.0.2022.0736

摘要/Abstract

摘要： 目的从减轻阻塞性睡眠呼吸暂停(OSA)诱发房颤大鼠心脏氧化应激角度探讨硫化氢外源性供体硫氢化钠的作用机制,为其治疗房颤提供科学依据。方法 24只雄性SD大鼠,随机分为对照组、模型组和硫氢化钠干预组,每组8只;各组大鼠均在麻醉状态下行气管插管,模型组和硫氢化钠组采用循环憋气法模拟OSA过程。全程记录心脏电生理过程,实验结束后采集血液及左心房组织。采用硫代巴比妥酸法检测丙二醛含量;采用黄嘌呤氧化酶法检测超氧化物歧化酶活力;采用Western blotting法检测氧化应激指标还原型烟酰胺腺嘌呤二核苷酸(NADPH)氧化酶4和缝隙连接蛋白43的表达水平。结果与模型组相比,硫氢化钠干预组房颤诱发率减少、房颤持续时间缩短(P均<0.05);与对照组相比,模型组左心房组织中NADPH氧化酶4表达增高,丙二醛含量增加、超氧化物歧化酶活力降低,伴随缝隙连接蛋白43的表达降低,硫氢化钠干预后,NADPH氧化酶4表达抑制,丙二醛含量降低、超氧化物歧化酶活力增加,缝隙连接蛋白43表达增加(P均<0.05)。结论硫化氢可减轻阻塞性睡眠呼吸暂停诱发房颤心脏氧化应激损伤,从而降低房颤的发生维持,其作用机制与抑制NADPH氧化酶4蛋白激活,清除体内氧自由基,抑制脂质过氧化,继而上调缝隙连接蛋白43表达密切相关。

关键词: 心房颤动, 阻塞性睡眠呼吸暂停, 硫化氢, 还原型烟酰胺腺嘌呤二核苷酸氧化酶4

Abstract: Objective To investigate the mechanism of exogenous donor of hydrogen sulfide, NaHS, in the treatment of atrial fibrillation(AF)in rats with obstructive sleep apnea(OSA)induced oxidative stress. Methods A total of 24 male SD rats were randomly divided into control, model and NaHS groups, with 8 rats in each group. All rats were intubated under anesthesia. The model and NaHS groups simulated OSA process by circulating air holding method. The electrophysiological process of the heart was recorded throughout the experiment. Blood and left atrial tissue were collected after the experiment. The content of malondialdehyde was determined with thiobarbituric acid method. The activity of superoxide dismutase was detected with xanthine oxidase method. The expressions of oxidative stress indexes NADPH oxidase 4(Nox4)and connexin 43(Cx43)were detected with Western blotting. Results Compared with the model group, the NaHS group had reduced induction rate and duration of AF(P<0.05). Compared with the control group, the model group had increased expression of Nox4 and malondialdehyde, decreased superoxide dismutase activity, and decreased expression of Cx43. After NaHS intervention, Nox4 expression was inhibited, malondialdehyde content was decreased, superoxide dismutase activity was increased, and Cx43 expression was increased(P<0.05). Conclusion Hydrogen sulfide can reduce the oxidative stress injury of AF induced by OSA, thus reducing the occurrence and duration of AF. The mechanism is closely related to the inhibiting of Nox4 activation, scavenging of oxygen free radicals, inhibiting of lipid peroxidation, and up-regulating of Cx43 expression.

Key words: Atrial fibrillation, Obstructive sleep apnea, Hydrogen sulfide, NADPH oxidase 4

中图分类号:

R541.7

赵亚庆, 徐静雯,王晓,侯应龙,高梅. 基于氧化应激探讨硫化氢改善阻塞性睡眠呼吸暂停诱发房颤的作用机制[J]. 山东大学学报 (医学版), 2022, 60(12): 7-12.

ZHAO Yaqing, XU Jingwen, WANG Xiao, HOU Yinglong, GAO Mei. Mechanism of hydrogen sulfide in improving atrial fibrillation induced by obstructive sleep apnea based on oxidative stress[J]. Journal of Shandong University (Health Sciences), 2022, 60(12): 7-12.

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