参附注射液对大鼠机械通气相关性肺损伤的保护作用及其机制

目的 探讨参附注射液(Shenfu injection,SF)对大鼠机械通气(mechanical ventilation,MV)相关性肺损伤的保护作用及其机制. 方法 40只健康成年雄性Wister大鼠采用随机数字表法分为4组,每组10只:对照组(C组)、正常潮气量MV组(N组)、大潮气量MV组(L组)、大潮气量MV+SF处理组(SF组).C组保留自主呼吸;N组、L组和SF组MV4h,潮气量分别设置为8～10 ml/kg、40 ml/kg、40 ml/kg,SF组于MV前15 min静脉注射SF 10 ml/kg.实验结束处死动物,收集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF),测定BALF中总蛋白、IL-1β、IL-18和TNF-α的浓度;取肺组织,测量湿/干重比(wet/dry,W/D),采用免疫组化法检测肺组织NF-κB的表达,观察病理学改变并进行肺损伤评分. 结果 SF组BALF中TNF-α、IL-1β、IL-18浓度分别为(65±11)、(47±9)、(58±8) ng/L,较L组(99±7)、(69±7)、(86±7) ng/L明显降低(P＜0.05);SF组大鼠肺损伤评分、W/D、肺组织NF-κB光密度值分别为(8.5±1.8)分、(5.0±1.6)、(0.32±0.28),较L组(14.1±2.7)分、(5.5±1.8)、(0.54±0.33)均明显降低(P＜0.05). 结论 SF可减轻大鼠MV相关性肺损伤,其机制可能与SF抑制肺内NF-κB通路的活性且降低肺内炎性因子的释放有关.

Effect of Shenfu injection on ventilator-induced lung injury in rats and its mechanism

Objective To evaluate the effect of Shenfu injection (SF) on ventilator-induced lung injury in rats and its mechanism.Methods Forty adult male Wister rats were equally and randomly divided into 4 groups(n=10) using a random number table:control group(group C),normal tidal volume ventilation group(group N),large tidal volume ventilation group(group L),and large tidal volume ventilation+SF group (group SF).The spontaneous breathing of rats was maintained in group C,while the other rats were tracheostomized and mechanically ventilated for 4 h in group N,group L and group SF.Rats were killed at the end of the ventilation and was lavaged their left lung,then the bronchoalveolar lavage fluid (BALF) was collected for determination of the concentrations of protein,IL-1β,IL-18 and TNF-α.The lung tissues were removed for determination of the wet/dry (W/D) lung weight,and immunohistochemistry was used to detected the expression of NF-κB.The pathological changes of the lungs were determinated by using light microscope and the lung injury scores were also determinated.Results Compared with group SFTNF-α (65±11) ng/L,IL-1β (47±9) ng/L,IL-18 (58±8) ng/L],the protein expression level of IL-1β,IL-18 and TNF-α in BALF were significantly increased in group L TNF-α (99±7) ng/L,IL-1β (69±7) ng/L,IL-18 (86±7) ng/L](P＜0.05).W/D (5.0±1.6) in group SF were significantly decreased while W/D (5.5±1.8) in group L (P＜0.05).The protein expression level of NF-κB were (0.32±0.28) in group SF while (0.54±0.33) in group L.The protein expression level of NF-κB were significantly decreased in group SF (P＜0.05) and the pathological changes were also significantly reduced in group SF.Conclusions SF can reduce ventilator-induced lung injury in rats and its mechanism may be related to the inhibition of the activity of NF-κB pathway and reducing the release of inflammatory cytokines in the lungs.