右美托咪定对大鼠机械通气相关肺损伤时小窝蛋白-1表达的影响

Effect of dexmedetomidine on expression of caveolin-1 in rats with ventilator-induced lung injury

目的观察右美托咪定(Dex)对大鼠机械通气相关肺损伤(VILI)时小窝蛋白-1(Cav-1)表达的影响。方法30只SD大鼠随机分为3组,每组10只:对照组(C组)、VILI组(V组)、De x预注射+VILI组(DV组)。200μg De x溶解于40ml 0.9%氯化钠注射液中配置成5μg/ml Dex注射液;DV组大鼠按1ml/kg经股静脉注射Dex注射液,C组、V组注射等量的0.9%氯化钠注射液;然后DV组以1ml/(kg·h)的速率持续静脉泵注Dex注射液,C组、V组以相同速率持续静脉泵注0.9%氯化钠注射液。20min后麻醉大鼠行气管插管术,C组保留自主呼吸,V组、DV组予机械通气(设置通气频率40次/min、潮气量40ml/kg、吸呼比1:1、吸入气中的氧浓度分数21%)制备模型,4h后处死大鼠取右肺组织计算湿干比(W/D),在光镜下进行肺组织病理学观察并测定肺损伤定量评价指标(IQA);左肺灌洗,制备并收集全部支气管肺泡灌洗液(BALF),检测BALF中clara细胞分泌蛋白16(CC-16)及炎症因子浓度;检测右侧肺组织Cav-1、Toll样受体4(TLR4)、核因子-κB(NF-κB)蛋白及mRNA相对表达量。结果与C组比较,V组、DV组IQA、W/D,CC-16、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6浓度,TLR4、NF-κB蛋白及mRNA相对表达量均明显升高(均P<0.05),Cav-1蛋白及mRNA相对表达量均明显降低(均P<0.05);与V组比较,DV组IQA、W/D,CC-16、TNF-α、IL-1β、IL-6浓度,TLR4、NF-κB蛋白及mRNA相对表达量均明显下降(均P<0.05),Ca v-1蛋白及mRNA相对表达量均明显升高(均P<0.05)。结论De x能减轻大鼠VILI程度,可能与上调Ca v-1表达有关。

Objective To investigate the effect of dexmedetomidine on the expression of caveolin-1 in rats with ventilator-induced lung injury.Methods Thirty adult male SD rats were randomly divided into control group(group C),ventilator-induced lung injury group(group V)and dexmedetomidine pre-treatment group(group DV)with 10 rats in each group.Ventilation-induced lung injury model was established in group V and group DV.Intravenous injection of Dex 1ml/kg was given to rats in group DV before and during the ventilation,while rats in group C and group V were injected with the same volume of 0.9%sodium chloride solution.The rats in group C kept spontaneous breathing,while rats in groups V and DV were anesthetized,tracheostomized and mechanically ventilated for 4h(breath rate 40/min,with tidal volume of 40ml/kg,inspiratory/expiratory ratio 1:1,and 21%oxygen).All rats were sacrificed at the end of experiments,the right lung was removed to calculate dry weight ratio(W/D ratio)and examine histologic lung injury(IQA)under light microscopy;the left lung was lavaged,and the contents of CC-16,tumor(TNF-α,IL-1β,IL-6 in lavage fluid were measured,the protein and mRNA expression of Cav-l,TLR4 and NF-κB were detected.Results In contrast of group C,IQA,W/D ratio,and the expression of CC-16,IL-1β,IL-6,TNF-α,TLR4 and NF-κB were significantly increased in the group V and group DV(P<0.05),while the Cav-l protein and mRNA expression was significantly declined(P<0.05).Compared with group V,IQA,W/D ratio,expression of CC-16,IL-1β,IL-6,TNF-α,TLR4 and NF-κB in group DV descended significantly(P<0.05),but the relative expression of Cav-l protein and mRNA was elevated dramatically(P<0.05).Conclusion Dexmedetomidine can relieve the degree of ventilation-induced lung injury in rats,which may be related to the up-regulation of Cav-1.