利多卡因对急性肺损伤模型大鼠肺组织线粒体自噬的影响

doi:10.16352/j.issn.1001-6325.2023.09.1394

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (9): 1394-1398.doi: 10.16352/j.issn.1001-6325.2023.09.1394

利多卡因对急性肺损伤模型大鼠肺组织线粒体自噬的影响

徐桂萍^1*, 陈雪莹², 张宇轩¹, 麦丽帕特·伊力艾克拜尔¹

1.新疆维吾尔自治区人民医院麻醉科新疆麻醉管理临床医学研究中心,新疆乌鲁木齐 830000;
2.新疆医科大学研究生学院,新疆乌鲁木齐 830000

收稿日期:2022-12-02 修回日期:2023-02-27 出版日期:2023-09-05 发布日期:2023-09-01
通讯作者: ^*xgpsyl@126.com

Effects of lidocaine on mitophagy in lung tissues of rat models with acute lung injury

XU Guiping^1*, CHEN Xueying², ZHANG Yuxuan¹, Malipate·YILIAIKEBAIER¹

1. Department of Anesthesiology, People's Hospital of Xinjiang Uygur Autonomous Region,Xinjiang Clinical Research Center forAnesthesia Management, Urumqi 830000;
2. Graduate School, Xinjiang Medical University,Urumqi 830000, China

Received:2022-12-02 Revised:2023-02-27 Online:2023-09-05 Published:2023-09-01
Contact: ^*xgpsyl@126.com

摘要/Abstract

摘要： 目的探讨利多卡因对急性肺损伤(ALI)大鼠肺组织线粒体自噬的影响。方法将大鼠分为对照组(control组)、急性肺损伤组[ALI组:腹腔注射10 mg/kg脂多糖(LPS)]和利多卡因干预组[lidocaine组:注射LPS后立即尾静脉给予10 mg/kg负荷剂量的利多卡因,再以10 mg/(kg·h^-1)的剂量持续泵注3 h]。造模24 h后处死大鼠,采血行血气分析并计算氧合指数(OI);随后立即开胸取左肺组织标本,Western blot测定肺组织中线粒体自噬相关蛋白E3泛素连接酶(Parkin)、微管相关蛋白1轻链3(LC3)和p62的表达,并计算LC3-Ⅱ/LC3-Ⅰ。HE染色观察右上肺组织病理变化,透射电镜下观察右下肺组织内线粒体自噬情况。结果与对照组比较,ALI组和lidocaine组的Parkin、LC3-Ⅱ/LC3-Ⅰ和PaCO₂水平升高(P＜0.05),PaO₂、OI、pH、p62水平降低(P＜0.05);与ALI组比较,lidocaine组的Parkin、LC3-Ⅱ/LC3-Ⅰ水平降低(P＜0.05),PaO₂、OI、pH、p62的水平回升(P＜0.05);光镜显示对照组大鼠肺泡结构完整、细胞形态正常;ALI组大鼠肺组织炎性反应细胞浸润、间隔增厚且肺泡塌陷;Lidocaine组损伤程度较ALI组减轻。电镜显示对照组肺组织及线粒体结构正常;ALI组肺组织细胞明显肿胀、有空泡形成,可见线粒体自噬小体的出现;Lidocaine组损伤程度较ALI组减轻。结论利多卡因可以减轻急性肺损伤,其机制可能与抑制线粒体自噬过度激活有关。

关键词: 利多卡因, 急性肺损伤, 线粒体, 自噬小体

Abstract: Objective To investigate the effect of lidocaine on mitophagy in model rat of acute lung injury(ALI). Methods The rats were divided into the control group, acute lung injury group (group ALI:intraperitoneal injection of 10 mg/kg of lipopolysaccharide(LPS) and lidocaine intervention group (group lidocaine:after intraperitoneal injection of LPS,receiving a loading dose of lidocaine of 10 mg/kg and continued for 3 h with dosage of 10 mg/kg per hour). The rats were sacrificed 24 hrs after LPS, blood was collected for blood gas analysis, and calculated for oxygenation index (OI).Thoracotomy was performed immediately after blood collection, the samples of left lung tissue were collected to determine the expression of mitophagy-related protein E3 ubiquitin ligase (Parkin), microtubule-associated protein 1 light chain 3 (LC3) and p62 by Western blot, and then LC3-Ⅱ/LC3-Ⅰ was calculated. After-wards, right-upper lung tissue structure was microscopy and the mitochondrial autophagy in the right lower lung tissue was examined by transmission electron microscopy. Results Compared with control group, the level of Parkin, LC3-Ⅱ/LC3-Ⅰ and PaCO₂ was increased in both group ALI and group lidocaine(P＜0.05),while PaO₂,OI,pH and p62 were decreased(P＜0.05). Compared with group ALI,the level of Parkin and LC3-Ⅱ/LC3-Ⅰ was decreased in group of lidocaine intervention (P＜0.05),while PaO₂,OI,pH and p62 were increased(P＜0.05).The results of light microscopy showed intact alveolar structure and normal cell morphology in group control, inflammatory cell infiltration, interval thickening and alveolar collapse were found in group ALI, and less degree in group lidocaine than in group ALI. Transmission electron microscopy showed that the lung tissue and mitochondrial structure were normal in group control; in group ALI, the lung tissue cell was found to be swollen and formed with physalides companying by mitochondrial autophagosomes; The degree of injury in group lidocaine was decreased as compared with group ALI. Conclusions Lidocaine attenuates acute lung injury and the mechanism may be related to inhibition of mitophagy hyperactivation.

Key words: lidocaine, acute lung injury, mitochondria, autophagosome

中图分类号:

R614

徐桂萍, 陈雪莹, 张宇轩, 麦丽帕特·伊力艾克拜尔. 利多卡因对急性肺损伤模型大鼠肺组织线粒体自噬的影响[J]. 基础医学与临床, 2023, 43(9): 1394-1398.

XU Guiping, CHEN Xueying, ZHANG Yuxuan, Malipate·YILIAIKEBAIER. Effects of lidocaine on mitophagy in lung tissues of rat models with acute lung injury[J]. Basic & Clinical Medicine, 2023, 43(9): 1394-1398.

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参考文献

[1]Swenson KE, Swenson ER. Pathophysiology of acute respiratory distress syndrome and COVID-19 lung injury[J]. Crit Care Clin, 2021,37:749-776.
[2]Schirris TJJ, Jansen J, Mihajlovic M, et al. Mild intracellular acidification by dexamethasone attenuates mitochondrial dysfunction in a human inflammatory proximal tubule epithelial cell model.[J]. Scientific reports, 2017,7:10623. doi:10.1038/s41598-017-10483-y.
[3]Xing W, Yang L, Peng Y, et al. Ginsenoside Rg3 attenuates sepsis-induced injury and mitochondrial dysfunction in liver via AMPK-mediated autophagy flux[J]. Bioscience reports, 2017,37:R20170934. doi:10.1042/BSR20170934.
[4]Wang Y, Mao X, Chen H, et al. Dexmedetomidine alleviates LPS-induced apoptosis and inflammation in macrophages by eliminating damaged mitochondria via PINK1 mediated mitophagy[J]. Int Immunopharmacol, 2019,73:471-481.
[5]Letsiou E, Sammani S, Wang H, et al. Parkin regulates lipopolysaccharide-induced proinflammatory responses in acute lung injury[J]. Transl Res, 2017,181:71-82.
[6]Zhang Z, Chen Z, Liu R, et al. Bcl-2 proteins regulate mitophagy in lipopolysaccharide-induced acute lung injury via PINK1/Parkin signaling pathway[J]. Oxid Med Cell Longev, 2020,2020:6579696. doi:10.1155/2020/6579696.
[7]Izdebska M, Halas-Wisniewska M, Zielinska W, et al. Lidocaine induces protective autophagy in rat C6 glioma cell line[J]. Int J Oncol, 2019,54:1099-1111.
[8]徐桂萍, 麦丽帕特·伊力艾克拜尔, 张宇轩, 等. 利多卡因对脓毒症大鼠肺损伤的影响[J]. 临床麻醉学杂志, 2021,37:1293-1296.
[9]刘秀洁, 王新雨, 宋正阳, 等. 细胞自噬在大鼠Ⅱ型肺泡上皮细胞低氧/复氧损伤中的作用[J]. 基础医学与临床, 2021,41:1440-1445.
[10]Dai XG, Xu W, Li T, et al. Involvement of phosphatase and tensin homolog-induced putative kinase 1-Parkin-mediated mitophagy in septic acute kidney injury[J]. Chin Med J (Engl), 2019,132:2340-2347.
[11]Jia L, Hu Y, Yang G, et al. Puerarin suppresses cell growth and migration in HPV-positive cervical cancer cells by inhibiting the PI3K/mTOR signaling pathway[J]. Exp Ther Med, 2019,18:543-549.
[12]Chen H, Lin H, Dong B, et al. Hydrogen alleviates cell damage and acute lung injury in sepsis via PINK1/Parkin-mediated mitophagy[J]. Inflamm Res, 2021,70:915-930.
[13]Long D, Chen Y, Qu L, et al. Lidocaine inhibits the proliferation and migration of endometrial cancer cells, and promotes apoptosis by inducing autophagy[J]. Oncol Lett, 2022,24:347. doi:10.3892/ol.2022.13467.
[14]Springer MZ, Macleod KF. In brief: mitophagy: mechanisms and role in human disease[J]. J Pathol, 2016,240:253-255.
[15]Kirkin V. History of the selective autophagy research: how did it begin and where does it stand today?[J]. J Mol Biol, 2020,432:3-27.

利多卡因对急性肺损伤模型大鼠肺组织线粒体自噬的影响

Effects of lidocaine on mitophagy in lung tissues of rat models with acute lung injury

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