右美托咪定减轻呼吸机相关性肺损伤模型大鼠肺组织损伤  

Dexmedetomidine alleviates lung tissue injury of rat models with ventilator-associated lung injury

作　　者：韩惠晶 吴红[1] 葛银 乔娟[1] HAN Huijing;WU Hong;GE Yin;QIAO Juan(Department of Anesthesiology,Jiangsu Subei People′s Hospital,Yangzhou 225001,China)

机构地区：[1]江苏省苏北人民医院麻醉科,江苏扬州225001

出　　处：《基础医学与临床》2024年第3期339-345,共7页Basic and Clinical Medicine

基　　金：扬州市科技计划项目(YZ2021235)。

摘　　要：目的探讨右美托咪定(DEX)对呼吸机相关性肺损伤(VILI)大鼠肺组织Ras同源基因家族成员A(RhoA)/Rho激酶1(ROCK1)信号通路的影响。方法建立VILI大鼠模型,将大鼠分为对照组(control组)、模型组(VILI组)、右美托咪定低、高剂量组(DEX-L、DEX-H组)、右美托咪定高剂量+溶血磷脂酸(LPA)组(DEX-H+LPA组)。测定大鼠肺组织湿/干质量比值(W/D);HE染色观察肺组织病理形态;ELISA试剂盒检测支气管肺泡灌洗液(BALF)中肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)的水平;TUNEL染色法检测肺上皮细胞死亡;Western blot检测细胞凋亡相关蛋白及RhoA、ROCK1表达水平。结果DEX可以减轻VILI大鼠肺损伤,降低肺损伤评分、W/D、细胞凋亡率和TNF-α、IL-1β、IL-6水平及Bax、cleaved caspase-3、RhoA、ROCK、α-SMA表达(P<0.05),升高Bcl-2表达(P<0.05);LPA可以促使大鼠肺损伤加重,肺损伤评分、W/D、细胞凋亡率和TNF-α、IL-1β、IL-6水平及Bax、cleaved caspase-3、RhoA、ROCK、α-SMA表达升高(P<0.05),Bcl-2表达降低(P<0.05)。结论右美托咪定可能通过抑制RhoA/ROCK1通路保护大鼠呼吸机相关性肺损伤。Objective To investigate the effect of dexmedetom idine(DEX)on lung tissue and Ras homolog gene family member A(RhoA)/Rho kinase 1(ROCK1)signaling pathway in lung tissue of rats with ventilator-induced lung injury(VILI).Methods A VILI rat model was established and separated into control group,model group(VILI group),dexmedetomidine low and high dose groups(DEX-L,DEX-H group),and high dose dexmedetomidine+lysophosphatidic acid(LPA)group(DEX-H+LPA group).Determination of wet/dry mass ratio of rat lung tissue(W/D);HE staining microscopy was applied to observe morphology of lung tissue;ELISA kit was applied to detect the level of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)in bronchoalveolar lavage fluid(BALF);TUNEL staining method was applied to detect lung epithelial cell death;Immunoblotting was applied to detect the expression levels of apoptosis-related proteins,and RhoA,ROCK1 proteins.Results DEX could reduce lung injury,lung injury score,W/D,apoptosis rate,levels of TNF-α,IL-1β,IL-6,and expression of Bax,cleaved caspase-3,RhoA,ROCK,α-SMA in VILI rats(P<0.05),while increased the expression of Bcl-2(P<0.05);LPA could aggravate lung injury and increase lung injury score,W/D,apoptosis rate,level of TNF-α,IL-1β,IL-6 and expressions of Bax,cleaved caspase-3,RhoA,ROCK andα-SMA(P<0.05);Bcl-2 expression level was decreased(P<0.05).Conclusions Dexmedetomidine may protect rats with ventilator-induced lung injury by the inhibition of RhoA/ROCK1 signaling pathway.

关 键 词：右美托咪定 呼吸机相关性肺损伤 Ras同源基因家族成员A/Rho激酶1(RhoA/ROCK1)信号通路 

分 类 号：R563.9[医药卫生—呼吸系统]