麦角甾醇对LPS诱导的肺损伤小鼠的抗炎作用研究

摘要

目的 研究麦角甾醇对LPS诱导的小鼠急性肺损伤的抗炎作用研究.方法 取50只雄性BABL/c小鼠随机分为5组:空白对照组、模型组、地塞米松组(2 mg/kg)、麦角甾醇低剂量组(20 mg/kg)、麦角甾醇高剂量组(40 mg/kg).空白对照组和模型组按体积给予生理盐水,地塞米松组(2 mg/kg)、麦角甾醇组(20、40 mg/kg)灌胃给予相应药物.给药1h后,除空白对照组,其余各组小鼠气管滴注20 μg LPS.检测小鼠肺干湿重比(W/D),肺泡灌洗液(BALF)中超氧化物歧化酶(SOD)水平、丙二醛(MDA)含量,血清与肺泡灌洗液炎性细胞因子(TNF-oα、IL-1β、IL-6)水平.取各组小鼠肺组织做HE染色,并检测肺组织Rho、ROCK1、ROCK2、p-NF-κBP65、NF-κBP65、p-IκBoα、IκBα蛋白表达.结果 麦角甾醇20、40 mg/kg能显著提升LPS诱导的急性肺损伤小鼠血清SOD水平,降低MDA含量;改善血清及肺泡灌洗液炎症因子水平和肺组织病理学改变;降低肺组织Rho、ROCK1、ROCK2、p-NF-κBP65、p-IκB α蛋白表达.结论 麦角甾醇对LPS诱导的急性肺损伤小鼠有保护作用,其作用可能与Rho/ROCK/NF-κB信号通路有关.%Objective To investigate the anti-inflammatory effect of ergosterin on lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods Totally 50 BABL/c mice were divided into 5 groups randomly:control group,model group,dexamethasone group (2 mg/kg),ergosterin (20 mg/kg),ergosterin (40 mg/kg).The mice were given ergosterin or dexamethasone at 1 h before intratracheal instillation of LPS.The lung wet-to-dry weight (W/D) ratio,the level of super oxide dismutase (SOD) and the content of malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF),and the levels of tumor necrosis factor-oα (TNF-α),interleukin-1 β (IL-1 β) and interleukin-6 (IL-6) in BALF were detected.The protein expression of Rho,ROCK1,ROCK2,p-NF-κBP65,NF-κBP65,p-IκBoα and IκBα in lung tissue was analyzed.Results Ergosterin of 20 mg/kg and 40 mg/kg could increase the level of SOD and decrease the content of MDA,and improve the levels of pro-inflammatory cytokines in serum and BALF and pathological changes.It could also decrease the protein expression of Rho,ROCK1,ROCK2,p-NF-κBP65 and p-IκBα in lung tissue.Conclusion Ergosterin can ameliorate the LPS-induced acute lung injury in mice and its related mechanism might be related to inhibition of Rho/ROCK/NF-κB pathway.