奥拉帕利对内毒素致急性肺损伤小鼠的保护作用  

Protective effect of Olaparib against acute lung injury induced by endotoxin in mice

作　　者：耿焱玲 朱丽丽[2] 李喜梅[2] 宋璐[2] 骆宇琛 徐钰行 弓清梅[1,2] GENG Yanling;ZHU Lili;LI Ximei;SONG Lu;LUO Yuchen;XU Yuhang;GONG Qingmei(Department of Critical Medicine,Fifth Clinical Medical College of Shanxi Medical University,Taiyuan 030012,China;Department of Critical Medicine,Shanxi Provincial People′s Hospital)

机构地区：[1]山西医科大学第五临床医学院重症医学科,太原030012 [2]山西省人民医院重症医学科

出　　处：《山西医科大学学报》2024年第5期560-567,共8页Journal of Shanxi Medical University

基　　金：山西省青年科学研究项目自由探索类项目(202203021212075)。

摘　　要：目的探讨奥拉帕利对内毒素致急性肺损伤小鼠的保护作用。方法24只SPF级雄性C57BL/6小鼠,8~10周龄,体质量20~30 g,按随机数字表法分为4组(n=6):control组、脂多糖(lipopolysaccharide,LPS)组、5 mg/kg奥拉帕利组和10 mg/kg奥拉帕利组。LPS组、5 mg/kg奥拉帕利组和10 mg/kg奥拉帕利组采用1 mg/mL LPS雾化构建ALI模型,每天30 min,连续3 d。5 mg/kg奥拉帕利组和10 mg/kg奥拉帕利组在第3天雾化后,即刻分别腹腔注射5,10 mg/kg奥拉帕利;control组腹腔注射等量生理盐水。给药后观察小鼠行为改变等一般情况,并于给药后24 h后处死小鼠,检测肺湿/干重比;BCA法分别测定血清和肺泡灌洗液总蛋白的含量,计算肺通透性指数(lung pemeability index,LPI);ELISA法测肺组织和血清IL-6、TNF-α、IL-1β的浓度;酶比色法测肺组织脂质过氧化丙二醛(malondialdehyde,MDA)和总抗氧化能力(total antioxidant capacity,T-AOC)的含量、超氧化物歧化酶(superoxide dismutase,SOD)和髓过氧化物酶(myeloperoxidase,MPO)的活性;HE染色测定肺组织损伤程度评分;免疫组化评估肺组织Caspase-1的表达水平。结果腹腔注射奥拉帕利后可见小鼠均存活,精神较前无明显烦躁及萎靡,无恶心、呕吐、腹泻、食欲减退等症状。与control组比较,LPS组、5 mg/kg奥拉帕利组和10 mg/kg奥拉帕利组肺湿/干比、LPI显著升高(P<0.05),肺组织和血清IL-6、TNF-α、IL-1β浓度显著升高(P<0.05),肺组织MDA的含量和MPO的活性显著升高(P<0.05),肺组织SOD的活性和T-AOC的含量显著下降(P<0.05),肺组织Caspase-1的表达水平显著升高(P<0.05),肺组织病理学损伤评分显著升高(P<0.05)。与LPS组比较,5 mg/kg奥拉帕利组和10 mg/kg奥拉帕利组肺湿/干比、LPI显著降低(P<0.05),肺组织和血清IL-6、TNF-α、IL-1β浓度显著降低(P<0.05),肺组织MDA的含量和MPO的活性显著降低(P<0.05),SOD的活性和T-AOC的含量显著升高(P<0.05),Caspase-1的表达水平显著降低(P<0.0Objective To evaluate the protective effect of Olaparib against endotoxic-induced acute lung injury in mice.Methods Twenty-four SPF male C57BL/6 mice,aged 8-10 weeks,weighing 20-30 g,were divided into four groups(n=6):control group,lipopolysaccharide(LPS)group,5 mg/kg Olaparib group and 10 mg/kg Olaparib group.The ALI model was constructed by nebulisation of 1 mg/mL LPS for 30 min per day for 3 d in LPS group,5 mg/kg Olaparib group,and 10 mg/kg Olaparib group.The mice in 5 mg/kg Olaparib group and 10 mg/kg Olaparib group were respectively injected intraperitoneally with 5,10 mg/kg Olaparib immediately after the nebulisation on the 3rd day.The mice in control group were injected intraperitoneally with an equal amount of saline.The beha-vioural changes and other general conditions of mice were observed after drug administration,and the mice were executed at 24 h after the administration.The wet/dry weight ratio of lung was calculated.The total protein content in serum and alveolar lavage fluid was determined using BCA method,and the lung permeability index(LPI)was calculated.The concentrations of IL-6,TNF-α,and IL-1βin lung tissues and serum were measured using ELISA.Additionally,enzyme colorimetry was used to measure the contents of malondialdehyde(MDA)and total antioxidant capacity(T-AOC),and the activities of superoxide dismutase(SOD)and myeloperoxidase(MPO)in lung tissues.The degree of lung tissue injury was determined using HE staining,and the level of Caspase-1 expression in lung tissues was assessed using immunohistochemistry.Results After intraperitoneal injection of Olaparib,all the mice survived,no obvious irritability or malaise were found,and no symptoms such as nausea,vomiting,diarrhea and loss of appetite were observed.Compared with control group,lung wet/dry ratio and LPI were significantly increased in LPS group,5 mg/kg Olaparib group and 10 mg/kg Olaparib group(P<0.05),the levels of IL-6,TNF-αand IL-1βwere significantly increased in lung tissue and serum(P<0.05),the content of MDA and the activ

关 键 词：奥拉帕利 急性肺损伤 细胞焦亡 氧化应激 脂多糖 

分 类 号：R563[医药卫生—呼吸系统]