肝X受体在百草枯致急性肺损伤小鼠肺组织中的表达及作用

摘要

目的：研究肝X受体（ Liver X receptors，LXRs）在百草枯（ Paraquat，PQ）致急性肺损伤小鼠肺组织中的表达情况及保护作用。方法48只雄性c57小鼠随机分为6组，对照组：0.1mL生理盐水腹腔注射；A组（ TO901317低剂量对照组）：5 mg／kg TO901317腹腔注射；B组（ TO901317高剂量对照组）：20 mg／kg TO901317腹腔注射；C组（百草枯染毒组）：百草枯28 mg／kg腹腔注射；D组（ TO901317低剂量预处理组）：百草枯染毒前0.5 h 给予TO9013175 mg／kg腹腔注射；E组（ TO901317高剂量预处理组）：百草枯染毒前0.5 h给予TO90131720 mg／kg腹腔注射。在百草枯染毒后72 h处死小鼠，收集肺组织及肺泡灌洗液标本。肺组织取出后测定肺湿重／干重比，肺组织切片后HE 染色进行肺损伤评分，采用ELISA方法检测肺泡灌洗液中IL-1β和TNF-α含量， Western blot 方法检测肺组织中LXRs（ LXRα和 LXRβ）及Toll样受体4（ TLR-4）的表达。结果对照组小鼠肺组织中可检测到较高水平的LXRα和 LXRβ表达，与对照组相比，百草枯中毒组小鼠LXRα和 LXRβ表达明显减少，肺湿重／干重比及肺损伤评分显著增加，肺泡灌洗液中 IL-1β和TNF-α含量明显增高，TLR-4表达明显增加。上述改变在TO901317预处理组明显减轻，减轻程度与TO901317剂量有关。结论肝X受体可以在正常小鼠肺组织的中表达，百草枯中毒可显著抑制肝X受体在小鼠肺组织中表达，应用LXRs激动剂TO901317能明显减轻百草枯导致的小鼠急性肺损伤程度，这一作用可能与LXRs抑制TLR-4在肺组织中的表达有关。%Objective To study the expression and role of LXRs in the lung tissues of mice with paraquat-in-duced acute lung injury. Methods Totally 48 male c57 mice were randomly divided into six groups. Control group:0. 1 mL normal saline solution was administered intraperitoneally. Group A ( low dose TO901317 group ):TO901317 was administered intraperitoneally at a dose of 5 mg/kg. Group B( high dose TO901317 group):TO901317 was admin-istered intraperitoneally at a dose of 20 mg/kg. Group C( paraquat poisoning):paraquat was administered intraperitone-ally at a dose of 28 mg/kg. Group D( low dose TO901317 pretreatment group):TO901317 was administered intraper-itoneally at a dose of 5 mg/kg at 30 min before PQ administration. Group E( high dose TO901317 pretreatment group):TO901317 was administered intraperitoneally at a dose of 20 mg/kg at 30 min before PQ administration. The mice were sacrificed at 72 h after PQ administration and lung tissues and bronchoalveolar lavage fluid( BALF)were col-lected. The lung W/D ratios were evaluated at 72 h after PQ administration,histopathological changes in the lung tis-sues were determined by HE staining and lung injury scores,IL-1β and TNF-α levels in BALF were measured via ELISA assay kits;the expressions of LXRs and TLR-4 were measured by Western blot. Results High levels of expres-sion of LXRα and LXRβ were detected in the lung tissues of control group. Compared with control group,the expres-sion of LXRα and LXRβwas significantly reduced,the lung W/D ratios,lung injury scores,IL-1βand TNF-αlevels in BALF,and the expression of TLR-4 were significantly increased in PQ poisoning group. All these changes were attenu-ated dose-dependently in TO901317 pretreatment group. Conclusion LXRs can be expressed in the lung tissues of normal mice and PQ administration significantly reduces the expression of LXRs. TO901317( LXRs agonist)pretreat-ment markedly attenuates PQ-induced acute lung injury of mice. This effect may be associated with the inhibition of TLR-4 expression in the lung tissues by LXRs.