重组人白细胞介素35早期干预对脂多糖诱导大鼠急性肺损伤的保护作用研究

Study of Protective Effect of Recombinant Human Interleukin 35 on Acute Lung Injury Induced by Lipopolysaccharide in Rats

目的探讨重组人白细胞介素35(interleukin 35,IL-35)早期干预对脂多糖(lipopolysaccharide,LPS)诱导的大鼠急性肺损伤(acute lung injury,ALI)的保护作用。方法采用随机数字表法将40只雄性SD大鼠分成正常组、致伤组、对照组和治疗组,每组各10只(其中每个观察点5只)。正常组大鼠不作处理,其余3组大鼠麻醉后经暴露的气管滴注10 mg/kg LPS建立大鼠ALI模型。造模后,治疗组大鼠尾静脉注射重组人IL-352μg,每天给药1次,连续给药3天;对照组大鼠尾静脉注射同等剂量无菌生理盐水,每天1次,连续3天;正常组和致伤组大鼠不进行药物干预。观察各组大鼠干预后第1、3天肺组织病理学变化及评分、动脉血氧分压(arterial partial pressure of oxygen,PaO_(2))和二氧化碳分压(partial pressure of carbon dioxide,PCO_(2))变化。采用酶联免疫吸附分析(enzyme-linked immunosorbent assay,ELISA)法检测大鼠肺组织匀浆上清液中肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)和白细胞介素10(interleukin 10,IL-10)含量。结果与正常组比较,致伤组、对照组和治疗组大鼠建模后第1天的肺组织病理评分均显著升高、PaO_(2)显著降低(P均<0.05);治疗组大鼠第3天肺组织病理评分显著低于致伤组和对照组、PaO_(2)显著高于致伤组和对照组,致伤组、对照组和治疗组大鼠第3天PCO_(2)较正常组显著升高(P均<0.05)。与正常组相比,致伤组、对照组和治疗组大鼠第1、3天TNF-α、IL-10含量明显升高(P均<0.05);治疗组大鼠第1、3天TNF-α含量明显低于对照组(P均<0.05),第1天IL-10含量明显低于致伤组和对照组,但第3天IL-10含量明显高于致伤组和对照组(P均<0.05)。结论重组人IL-35具有减轻LPS致大鼠肺损伤的作用,可降低肺损伤组织TNF-α水平,提高IL-10水平的作用。

Objective To investigate the protective effect of early intervention of recombinant human interleukin(IL-35)on lipopolysaccharide(LPS)induced acute lung injury(ALI)in rats.Methods A total of 40 male SD rats were randomly divided into normal group,injury group,control group and IL-35 treatment group by random number table method,with 10 rats in each(5 rats at each observation point).The normal group was not treated,while the other 3 groups of rats were given 10 mg/kg LPS through exposed trachea after anesthesia to establish ALI model.After modeling,the rats in treatment group were injected with 2μg of recombinant human IL-35 through the tail vein once a day for 3 days;the control group was injected with the same dose of sterile saline via tail vein once a day for 3 consecutive days;the normal group and injury group did not inject any drugs.The pathological changes and scores of lung tissue,arterial partial pressure of oxygen(PaO_(2))and partial pressure of carbon dioxide(PCO_(2))of rats in each group were observed on the 1st and 3rd day after treatment.To detect content of tumor necrosis factor alpha(TNF-α)and interleukin 10(IL-10)in lung tissues of rats by enzyme-linked immunosorbent assay.Results Compared with normal group,the pathological scores of lung tissue in injury group,control group and treatment group were significantly increased and PaO_(2) was significantly decreased on the 1st day after modeling(all P<0.05);the pathological score of lung tissue in treatment group was significantly lower than that in injury group and control group,and the PaO_(2) was significantly higher than that in injury group and control group,and the PCO_(2) was significantly higher than that in normal group on the 3rd day(all P<0.05).Compared with normal group,the contents of TNF-αand IL-10 in injury group,control group and treatment group were significantly increased on 1st and 3rd days(all P<0.05);the TNF-αcontent in the treatment group was significantly lower than that in the control group on the 1st and 3rd days(all P<0.05),the IL-10 content was significantly lower than that in the injury group and the control group on the 1st day,but the IL-10 content was significantly higher than that in the injury group and the control group on the 3rd day(all P<0.05).Conclusion Recombinant human IL-35 can reduce LPS-induced lung injury,reducing the level of TNF-αin lung injury tissue and increasing the level of IL-10.