罗格列酮通过减少Th17细胞极化减轻LPS诱导的小鼠急性肺损伤

Rosiglitazone attenuates LPS-induced mice acute lung injury by reducing polarization of Th17 cells in mouse

目的探讨罗格列酮(RSG)对急性肺损伤(ALI)小鼠的作用及可能的机制。方法 24只BALB/c小鼠,随机分为对照组(control)、模型组(LPS)、罗格列酮干预组(RSG)和GW9662拮抗组(GW9662),每组6只。分别检测支气管肺泡灌洗液(BALF)中炎性细胞分类计数和炎性因子水平、HE染色观察肺组织病理改变,Q-PCR和Western blot分别检测Th17细胞核转录因子RORγt及PPARγ的mRNA和蛋白表达。结果与对照组比较,模型组BALF中性粒细胞比例和炎性因子水平均显著增高(P<0.05);肺组织RORγt高表达(P<0.05)。接受罗格列酮干预小鼠PPARγ明显增高,炎性反应指标均较模型组减轻(P<0.05),同时伴有RORγt表达降低。GW9662显著拮抗罗格列酮的保护作用,小鼠肺组织炎性反应显著,RORγt基因的mRNA和蛋白水平均较罗格列酮组回升(P<0.05)。结论罗格列酮可通过活化PPARγ,进而抑制Th17细胞的分化,减轻由LPS诱导的小鼠急性肺损伤。

Objective To investigate the effect of rosiglitazone（RSG） on acute lung injury （ALI） murine model and to explore the possible mechanism. Methods BLAB/e （n = 24） mice were randomized into control group, ALI model group, RSG group and GW9662 group. The percentage of the inflammation cells in the bronchoalveo- lar lavage fluid （BALF） and the histopathologieal changes of the lung tissues were examined to reflex the degree of inflammation. Meanwhile, the level of inflammatory eytokines was measured by ELISA. The expression of RORYt and PPARY at mRNA and protein level in the lung tissues was determined by RT-qPCR and Western blot respectively. Results Compared with control group, the percentage of neutrophils and the contents of the inflam- matory cytokines in LPS group were significantly increased in BALF （P 〈0. 05 ）. Meanwhile, elevated mRNA and protein levels of RORYt suggested an increased number of Thl7 cells. Compared with LPS group, the degree of lung inflammation decreased in RSG group accompanied with low expression of ROR＇yt and high expression of PPARY（P 〈 0.05）. GW9662 significantly antagonized the protective effect of rosiglitazone, showing obviousmouse lung tissue inflammation, and higher mRNA and protein levels of RORYt as compared with RSG group （P 〈 0.05）. Conclusions Rosiglitazone attenuates lung inflammation by reducing the polarization of Thl7 cells in a murine ALI model induced by LPS.