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

作　　者：徐桂萍[1] 陈雪莹 张宇轩[1] 麦丽帕特·伊力艾克拜尔 XU Guiping;CHEN Xueying;ZHANG Yuxuan;Malipate·YILIAIKEBAIER(Department of Anesthesiology,People′s Hospital of Xinjiang Uygur Autonomous Region,Xinjiang Clinical Research Center for Anesthesia Management,Urumqi 830000;Graduate School,Xinjiang Medical University,Urumqi 830000,China)

机构地区：[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

出　　处：《基础医学与临床》2023年第9期1394-1398,共5页Basic and Clinical Medicine

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PaCO 2水平升高(P<0.05),PaO 2、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),PaO 2、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。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-Ⅰwas 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-Ⅰand PaCO 2 was increased in both group ALI and group lidocaine(P<0.05),while PaO 2,OI,pH and p62 were decreased(P<0.05).Compared with group ALI,the level of Parkin and LC3-Ⅱ/LC3-Ⅰwas decreased in group of lidocaine intervention(P<0.05),while PaO 2,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

关 键 词：利多卡因 急性肺损伤 线粒体 自噬小体 

分 类 号：R614[医药卫生—麻醉学]