右美托咪定基于线粒体自噬对支气管肺发育不良模型鼠的保护作用机制研究  

The mechanism of protective effects of dexmedetomidine based on mitophagy in a broncho-pulmonary dysplasia model of mice

作　　者：冯越 向伟 周琼霖 才桁 张秋月 Feng Yue;Xiang Wei;Zhou Qionglin;Cai Heng;Zhang Qiuyue(Department of Pediatrics,the First Affiliated Hospital of Hainan Medical University,Haikou 570102,China;Department of Pediatrics,Hainan Women and Children's Medical Center,Haikou 570312,China;Hainan Medical University,Haikou 571199,China)

机构地区：[1]海南医科大学第一附属医院儿科,海口570102 [2]海南省妇女儿童医学中心儿科,海口570312 [3]海南医科大学,海口571199

出　　处：《中国小儿急救医学》2025年第1期44-49,共6页Chinese Pediatric Emergency Medicine

基　　金：国家自然科学基金(82060289);海南省自然科学基金(821RC708);海南省卫生健康行业科研项目(20A200276)。

摘　　要：目的探讨在高氧条件下,右美托咪定(Dex)基于线粒体自噬对支气管肺发育不良(BPD)模型鼠的保护作用机制。方法将新生大鼠随机分为空气对照组、高氧损伤组、Dex对照组和高氧+Dex组,每组各6只。空气对照组与Dex对照组暴露于空气中,高氧损伤组与高氧+Dex组暴露于90%O_(2)。在此基础上,Dex对照组与高氧+Dex组每日进行腹腔注射Dex 500μg/kg。7 d后收集肺组织样本,采用HE染色法观察肺组织的形态学变化;利用透射电镜观察新生大鼠肺组织I型上皮细胞线粒体的超微结构变化;测定新生大鼠肺组织中复合体Ⅰ(ComplexⅠ)的活性;通过qPCR评估新生大鼠肺组织中PTEN诱导假定激酶1(PINK1)和帕金蛋白(Parkin)的表达水平;采用Western blot技术检测肺组织中PINK1和Parkin的蛋白表达水平。结果透射电镜下观察到,空气对照组与Dex对照组的肺组织线粒体结构完整,而高氧损伤组的肺组织细胞线粒体结构严重受损,高氧+Dex组的线粒体损伤程度有所缓解。高氧损伤组的新生大鼠肺组织中氧化呼吸链ComplexⅠ的活性(4.824±0.804)显著低于空气对照组(15.276±0.804)及高氧+Dex组(9.648±0.804),差异均有统计学意义(均P<0.05)。经qPCR分析,高氧损伤组新生大鼠肺组织中PINK1和Parkin的表达水平(1.80±0.06、2.10±0.14)高于空气对照组(1.00±0.07、1.00±0.09),但低于高氧+Dex组(3.61±0.19、4.24±0.43),差异均有统计学意义(均P<0.05)。通过Western blot技术检测,高氧损伤组新生大鼠肺组织中PINK1和Parkin的表达水平(2.16±0.11、3.82±0.13)高于空气对照组(1.00±0.01、1.00±0.01),低于高氧+Dex组(3.35±0.14、5.48±0.15),差异均有统计学意义(均P<0.05)。此外,空气对照组与Dex对照组在透射电镜下线粒体结构完整程度、ComplexⅠ酶活性、qPCR分析后的PINK1和Parkin表达水平以及Western blot检测的PINK1和Parkin表达水平上,差异均无统计学意义(均P>0.05)。结论Dex能够改善BPD模Objective To explore the protective mechanism of dexmedetomidine(Dex)in a model of broncho-pulmonary dysplasia(BPD)in mice exposed to hyperoxia.MethodsNeonatal rats were randomly assigned to four groups:air control group,hyperoxia injury group,Dex control group,and hyperoxia+Dex group,with six animals in each group.The air control and Dex control groups were exposed to ambient air,while the hyperoxia injury and hyperoxia+Dex groups were exposed to 90%O_(2).The Dex control and hyperoxia+Dex groups received daily intraperitoneal injections of Dex at a dosage of 500μg/kg.Lung tissue samples were collected after 7 days.Histomorphological changes in lung tissue were evaluated using hematoxylin and eosin(HE)staining,and mitochondrial ultrastructural changes in type I epithelial cells of neonatal rat lung tissue were observed via transmission electron microscopy.The activity of ComplexⅠin neonatal rat lung tissue was assessed.The expression levels of PINK1 and Parkin in neonatal rat lung tissue were measured using quantitative PCR(qPCR).Western blot analysis was conducted to determine the protein expression levels of PINK1 and Parkin in lung tissues.ResultsUnder transmission electron microscopy,mitochondrial structures were intact in the lung tissues of both the air control group and the Dex control group.However,significant mitochondrial damage was observed in the hyperoxia injury group,while the hyperoxia+Dex group exhibited some relief from mitochondrial damage compared to the hyperoxia injury group.The activity of the oxidized respiratory chain ComplexⅠin the hyperoxia injury group was significantly lower than that in the air control group(4.824±0.804 vs.15.276±0.804,P<0.05)and the hyperoxia+Dex group(4.824±0.804 vs.9.648±0.804,P<0.05).After qPCR analysis,the expression levels of PINK1 and Parkin in the hyperoxia injury group were higher than those in the air control group(1.80±0.06 vs.1.00±0.07,2.10±0.14 vs.1.00±0.09,P<0.05),but lower than those in the hyperoxia+Dex group(1.80±0.06 vs.3.61±0.19,2.10�

关 键 词：支气管肺发育不良 线粒体 自噬 右美托咪定 PTEN诱导假定激酶1 帕金蛋白 

分 类 号：R726.1[医药卫生—儿科]