鸢尾素对脓毒症引发的急性肺损伤的影响及机制

郭红; 金屏; 刘金成; 杨剑; 陈亚武

doi:10.12125/j.chj.202204060

鸢尾素对脓毒症引发的急性肺损伤的影响及机制

Protective mechanism of Irisin in sepsis-induced acute lung injury

摘要

摘要:
目的探究鸢尾素（Irisin）在脓毒症（sepsis）诱导的急性肺损伤（acute lung injury，ALI）中的作用机制。
方法将C57小鼠以随机数字表法分为对照（Con）组、鸢尾素（Irisin）组、盲肠结扎（cecal ligation and puncture，CLP）组、CLP-Irisin组。将A549细胞分为对照（PBS）组、脂多糖（lipopolysaccharide，LPS）组、Irisin保护组（LPS-Irisin）、LPS-Irisin-尿石素A（urolithin A, UA）组、LPS-UA组、LPS-3-甲基腺嘌呤（3-Methyladenine, 3-MA）组。以CCK-8试剂盒检测细胞活力，并检测MPO、PaO₂/FiO₂、IL-1α、IL-6、TNF-α、H₂O₂、MDA、GSH-Px活力等，同时以Western blot方法分析线粒体自噬相关蛋白的表达情况。
结果在体研究表明，Irisin可通过调节线粒体自噬并降低肺组织炎性因子表达(P<0.05)与抑制氧化应激(P<0.05)，增加氧合指数并降低小鼠死亡率，进而缓解脓毒症导致的ALI。体外研究证实，LPS可显著降低A549细胞活力(P<0.05)，同时炎性因子表达增加与线粒体自噬异常。进一步的研究证实，Irisin处理可显著缓解LPS诱导的细胞损伤(P<0.05)，而urolithin A处理则部分抵消Irisin对细胞的保护作用(P<0.05)。
结论 Irisin通过调节Pink1/Parkin介导的线粒体自噬，维持线粒体功能，缓解脓毒症导致的ALI。

Abstract:
AIM To explore the mechanism of Irisin in sepsis-induced acute lung injury (ALI).
METHODS C57 mice were randomly divided into Con group, Irisin group, CLP Group and CLP-Irisin group. A549 cells were divided into Con group, LPS group, Irisin group (LPS-Irisin), LPS-Irisin-UA group, LPS-UA group and 3-MA group. CCK-8 kit was used to detect cell viability, MPO, PaO₂/FiO₂, IL-1α, IL-6, TNF-α, H₂O₂, MDA and GSH-Px activity and Western blot was used to analyze the expression of mitophagy related proteins.
RESULTS In vivo studies showed that Irisin alleviated sepsis-induced ALI by regulating mitophagy and reducing the expression of inflammatory factors in lung tissues (P<0.05). Meanwhile, the oxygen index was increased and the mortality rate of mice was decreased. In addition, Irisin resisted CLP-induced ALI by reducing oxidative stress (P<0.05). In vitro studies confirmed that LPS significantly reduced the viability of A549 cells and increased the expression of inflammatory factors and abnormal mitophagy (P<0.05). Irisin or 3-MA treatment significantly reduced LPS induced cell injury and UA treatment partially counteracted the protective effect of Irisin on A549 cells (P<0.05).
CONCLUSION Irisin alleviates sepsis-induced ALI by regulating Pink1/Parkin mediated mitophagy and maintaining mitochondrial functions.

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