右美托咪定对大鼠I/R损伤肺组织TLR4表达及保护作用的影响

Dexmedetomidine prevents inflammatory responses in injured rat lung tissues induced by ischemia/reperfusion through inhibition of TLR4 expression

目的:探讨右美托嘧啶对大鼠再灌注损伤肺组织Toll样受体素4(TLR4)表达的调控,并分析其对肺保护作用机制。方法:采用大鼠在体左侧肺缺血/再灌注(I/R)模型,50只健康雄性成年SD大鼠随机分为5组(n=10):对照组(Sham组)、缺血/再灌注组(I/R组)、右美托咪定组(Dex组)、阿替美唑组(Atip组)、右美托咪定+阿替美唑组(Dex+Atip组),实验结束后处死大鼠,留取左肺,检测肺湿干重比(W/D)和总肺水含量(TLW);光镜下观察肺组织形态结构变化;PCR检测肺组织TLR4 mRNA表达;Western blot检测肺组织TLR4的蛋白表达。结果:与Sham组相比,其余各组W/D和TLW明显升高(P<0.05,P<0.01),TLR4 mRNA和蛋白表达量上升(P<0.01),光镜显示肺组织结构出现明显损伤性变化;与I/R组相比,Dex组W/D和TLW下降(P<0.05,P<0.01),TLR4 mRNA和蛋白表达量降低(P<0.01),光镜下肺组织损伤减轻;与Dex组比较,Dex+Atip组W/D和TLW明显升高(P<0.05,P<0.01),TLR4 mRNA和蛋白表达量上升(P<0.01),光镜肺组织结构损伤严重;I/R组、Atip组、Dex+Atip组两两比较,以上各指标均无统计学差异(P>0.05)。结论:I/R可引起大鼠肺组织TLR4表达上调和肺组织损伤;右美托咪啶可减轻肺I/R损伤,抑制TLR4表达,这种作用与α2-肾上腺素能受体有关。

Objective： To investigate the effect of Dexmedetomidine （Dex） on Toll-like reeeptor 4（TLR4） expression in lung （luring lung ischemia/repeffusion（I/R） in rats and its possible protecting mechanisms. Methods： In vivo I/R model in left lung of SD rats was estahlished. Fifty aduh healthy male SD rats were randomly divided into five groups （n = 10）： control group （Sham group）, I/R group, Dex group, atipamezole group （Atip group） and Dex ＋ Atip group. After the I/R experiment, rats were killed and the left lung tissues were harvested to get the lung wet/dry weight（W/D）; Ultrastructure of lung tissue were observed under light microscopy; The mRNA expression of TLR4 in lung tissues were determined by RT-PCR; The protein level of TLR4 in lung tissues was detected by Western hlot. Results： ①Compared with those in the Sham group, W/D and total lung water content （TLW） in other groups increased significantly （P 〈 0.05）, the mRNA and protein expression levels of TLR4 in lung tissues increased too. The structure damages of lung tissues observed under light microscopy in other groups were more than that of Sham group. ②Compared with those in the I/R group, W/D and TLW in the Dex group were lower （ P 〈 0.05, P 〈 0.01 ）, the mRNA and protein expression levels of TLR4 in lung tissues decreased （ P 〈 0.01 ）, and reduced structure damages of lung tissues were observed under light microscopy in Dex group. @Compared with those in the Dex group, W/D and TLW in the Dex ＋ Atip group were higher （P 〈 0.01 ）, the mRNA and protein expression levels of TLR4 in lung tissues increased （P 〈 0.01 ）, and the structure damages of lung tissues observed under light microscopy were more serious. There was no significant difference of the above parameters among I/R, Atip,Dex ＋ Atip groups. Conclusion： Lung isehemia/repeffusion eansed high expression of TLR4 and finally induced damages of the lung. Dexmedetomidine could inhibit TLR4 expression and ＇alleviate the lung ischemia/repeffusion injmy, which was related to activation of α2-adreno receptor.