TO901317对百草枯致小鼠急性肺损伤的保护作用  

Protective effect of TO901317 against paraquat - induced acute lung injury of mice

作　　者：胡晓[1] 贾冬[1] 陈良宏[1] 王煜[1] 赵敏[1] 

机构地区：[1]中国医科大学附属盛京医院急诊科,辽宁沈阳110004

出　　处：《中国急救医学》2017年第9期834-838,F0003,共6页Chinese Journal of Critical Care Medicine

摘　　要：目的 研究肝X受体（liver X receptors, LXRs）激动剂TO901317在百草枯（paraquat,PQ）致小鼠急性肺损伤过程中的作用及可能的机制。方法 96只雄性c57小鼠随机分为4组,每组24只小鼠。对照组：给予小鼠0.1 mL生理盐水腹腔注射；PQ染毒组：给予小鼠PQ 28 mg/kg腹腔注射；TO901317低剂量处理组：小鼠PQ染毒30 min后给予TO901317 5 mg/kg腹腔注射；TO901317高剂量处理组：小鼠PQ染毒30 min后给予TO901317 20 mg/kg腹腔注射。分别在PQ染毒后6、12、24、72 h每组处死6只小鼠，收集小鼠肺组织及肺泡灌洗液（BALF）。肺组织切片HE染色后对比各组肺组织病理学改变，检测肺组织丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性，检测BALF中肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）含量，Western blot法检测肺组织核因子-κB（nuclear factor-kappa B, NF-κB）的表达情况。结果 与对照组比较，PQ染毒组小鼠肺组织病理损伤显著，肺组织MDA含量显著增高，SOD活性下降，BALF中TNF-α和IL-1β含量显著增高，NF-κB表达显著增加（P〈0.05）。与PQ染毒组比较，TO901317处理组小鼠肺组织损伤显著减轻，MDA、TNF-α和IL-1β含量下降，SOD活性上升，NF-κB表达显著下降（P〈0.05），且TO901317高剂量处理组效果更显著（P〈0.05）。结论 LXRs激动剂TO901317通过抑制NF-κB信号通路在小鼠肺组织的表达，显著减轻PQ诱导的小鼠急性肺损伤。Objective To investigate the effect and mechanism of TO901317, liver X receptors （LXRs） agonist, against paraquat （PQ） - induced acute lung injury. Methods A total of 96 e57 mice were randomly divided into 4 groups of 24 each. Control group ： mice were intraperitoneally injected with 0.1 mL normal saline solution. PQ group ： mice were intraperitoneally injected with PQ at a dose of 28 mg/kg. Low dose TO901317 group： mice were intraperitoneally injected with TO901317 at a dose of 5 mg/kg 30 rain after PQ exposure. High dose TO901317 group： mice were intraperitoneally injected with TO901317 at a dose of 20 mg/kg 30 min after PQ exposure. At 6, 12, 24, and 72 h after PQ administration, 6 mice in each group were sacrificed to collect the lung tissues and bronchoalveolar lavage fluid （BALF） for testing. Histopathology changes of lung tissues were measured by HE staining. Malondialdehyde （MDA） levels and superoxide dismutase （SOD） activities in lung tissues, TNF- α and IL - 1β levels in BALF were respectively detected in each group. Nuclear factor - kappa B （ NF - κB） expression in lung tissues were evaluated by Western blot. Results Compared with control group, PQ exposure induced severe lung tissue lesions （ P 〈 0. 05 ）. PQ exposure also significantly increased the levels of MDA, TNF - α and IL - 1β while decreased the activities of SOD （ P 〈 0.05 ）. Furthermore, PQ exposure markedly upregulated the expression of NF - κB in lung tissues （P 〈 0.05）. In comparison with PQ group, TO901317 treatment significantly alleviated lung tissue lesions, decreased the levels of MDA, TNF -α and IL - 1β, increased the activities of SOD, and downregulated the expression of NF - κB. Conclusion LXRs agonist TO901317 treatment significantly alleviates PQ -induced acute lung injury of mice by inhibition of NF - κB signaling pass way.

关 键 词：肝X受体(LXRs) T0901317 百草枯(PQ) 急性肺损伤 核因子-KAPPA B(NF—κB) 

分 类 号：R338.26[医药卫生—人体生理学]