氨溴索与肝素联合应用对急性肺损伤兔TNF-α和IL-1β的影响

目的：探讨联合应用氨溴索与小剂量肝素对急性肺损伤（ALI）时氧化应激,TNF-α和IL-1β变化的干预及其机制。方法：健康日本大耳白兔24只,随机分成3组（n=8）：①生理盐水对照组（NC）,②油酸损伤组（OA）,③氨溴索＋小剂量肝素治疗组（AH）。各组分别在给药前和给药后6 h采血及测定动脉血氧分压（PaO2）、肿瘤坏死因子-α（TNF-α）、白介素-1β（IL-1β）的含量,实验结束后肉眼观察肺病理改变,测定支气管肺泡灌洗液（BALF）以及肺组织匀浆中TNF-α、IL-1β、超氧化物歧化酶（SOD）、丙二醛（MDA）、黄嘌呤氧化酶（XO）、谷胱甘肽过氧化物酶（GSH-Px）的含量,检测肺组织原位凋亡细胞变化、肺组织湿干比（W/D）,光镜观察肺组织病理改变,电镜观察肺组织超微结构变化。结果：①光镜,电镜观察结果以及W/D提示氨溴索＋小剂量联合治疗减轻了ALI造成的肺组织形态学改变。②OA组中显著降低的PaO2均在AH组明显升高（P〈0.01）。③抗氧化指标GSH-Px和SOD活力检测,发现AH组比OA组有不同程度升高（P〈0.01或P〈0.05）,而氧化性指标XO活力和MDA含量则较OA组显著降低（P〈0.01）。④除给药前IL-1β外,在OA组中IL-1β、TNF-α含量均显著高于NC组（P均〈0.01）,但在AH组中有显著的降低（P〈0.01）。⑤AH组凋亡指数（AI）比OA组显著降低（P〈0.01）。结论：在OA致ALI时,TNF-α和IL-1β明显升高,参与了ALI的发生与发展。联合应用氨溴索与小剂量肝素可减轻氧化应激反应,抑制促炎细胞因子TNF-α和IL-1β释放,发挥对ALI的治疗作用。

Effects of ambroxol combined with low-dose heparin on TNF-α and IL-1β in rabbits with acute lung injury

Objective：To investigate the intervention and mechanism of ambroxol combined with low-dose heparin on oxidative stress,TNF-α and IL-1β in rabbits with acute lung injury（ALI）.Methods：Twenty-four healthy Japanese rabbits were randomly divided into three groups：①Normal saline control group（NC）,②Oleic acid injury group（OA）,③Ambroxol＋low-dose heparin therapy group（AH）. After the success of ALI model,AH group was injected ambroxol＋low-dose heparin,while the NC group and OA group were injected the same dose of normal saline by the same method.Arterial oxygen tension（PaO2）,tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） at different time points were determined.The pathological manifestation of both side lungs was observed at the end of expeiment.The activity of glutathione peroxidase（GSH-Px）,superoxide dismutase（SOD）,xanthine oxidase（XO） and the content of malondialdehyde（MDA） in bronchoalveolar lavage fluid（BALF） and lung tissue homogenate were tested.The apoptosis index was detected.The lung wet/dry（W/D） ratio was calculated.The pathological changes in lung tissue were observed by light microscopy,and the ultrastructural changes of lung tissue were observed by electron microscopy.Results：①The instructive injury induced by ALI observed under electron microscope and light microscope and W/D was decreased significantly in AH group.②PaO2 was improved significantly in AH group,compared with that in OA group（P0.01）.③The activity of GSH-Px and SOD in AH group increased significantly（P0.01 or P0.05） but the activity of XO and the content of MDA decreased significantly（P0.01）,compared with those in OA group.④Except the content of IL-1β in serum before treatment,the content of IL-1β and TNF-α in serum,BALF,lung tissue homogenate of OA group increased significantly（P0.01）,and those were obviously improved in AH group.⑤Apoptosis index（AI） in AH group decreased significantly（P0.01） compared with that in OA group.Conclusion：In ALI induced by OA,IL-1β and TNF-α increases significantly and involved in the occurrence and development of ALI.Ambroxol combined with low-dose heparin can reduce lung cells oxidative stress to inhibit the release of IL-1β and TNF-α,which play a role in the treatment of ALI.