解放军医学院学报2023，Vol.44Issue(12)：1391-1398,1409,9.DOI:10.12435/j.issn.2095-5227.2023.095
基于Wnt/β-catenin信号通路探讨羟氯喹对烟雾吸入致肺纤维化大鼠的作用机制
Mechanism of hydroxychloroquine's effect on pulmonary fibrosis after smoke inhalation in rats via Wnt/β-catenin signaling pathway
摘要
Abstract
Background Pulmonary fibrosis due to smoke inhalation is a common complication after fire,with high mortality rate and a lack of effective treatments,making it urgent to explore therapeutic agents and their mechanisms for this serious condition.Objective To investigate whether HCQ exerts anti-pulmonary fibrosis effect through inhibiting Wnt/β-catenin signaling pathway by constructing a rat model of pulmonary fibrosis following smoke inhalation induced acute lung injury(SI-ALI).Methods Totally 140 male SD rats were randomly divided into control group(C),model group(S),phosphate buffered saline group(S+PBS),methylprednisolone group(S+MP)and hydroxychloroquine group(S+HCQ),among which the S+HCQ group was divided into 3 subgroups according to different HCQ doses(5 mg/kg,10 mg/kg,20 mg/kg),with 20 rats in each group.Rats in each group were given intraperitoneal injections of corresponding doses of PBS,MP,and HCQ at 1 h before smoke inhalation in the chamber daily for 30 min and a total of 7 d,and continued to be housed normally until 28 d for comparison of survival rates and lung histopathological changes among rats in each group;The mRNA and protein levels of α-SMA,Col Ⅰ/Ⅲ,β-catenin and p-GSK-3β/GSK-3β were detected in rat lung tissues by qRT-PCR and western blotting.Results Compared with the C group,the survival rate of rats in the S group and S+PBS group decreased significantly after smoke inhalation,and the survival rate remained at 70％after 72 h(P<0.05),and the pathology suggested an increase in pulmonary fibrosis.Compared with the S+PBS group,the survival rate of rats in the S+MP group and S+HCQ group increased and the degree of pulmonary fibrosis decreased,with 20 mg/kg HCQ and 4 mg/kg MP having obvious effects on the survival rate(90％and 95％),but only the 4 mg/kg MP group showed significant difference.Western blot results indicated that the expression of Collagen Ⅰ,Collagen Ⅲ,α-SMA and core protein β-catenin and p-GSK-3β/GSK-3β in Wnt/β-catenin signaling pathway in rat lung tissues decreased after HCQ and MP intervention(P<0.05),with 20 mg/kg HCQ having the most significant inhibitory effect on the proteins(P＜0.05).qRT-PCR results were generally consistent with western blot.Conclusion HCQ has a protective effect on pulmonary fibrosis after smoke inhalation in rats,and the best effects are observed at 20 mg/kg HCQ,where part of the protective mechanism may be achieved through inhibition of the Wnt/β-catenin signaling pathway.关键词
烟雾吸入/肺纤维化/羟氯喹/Wnt/β-catenin信号通路/甲基泼尼松龙Key words
smoke inhalation/pulmonary fibrosis/hydroxychloroquine/Wnt/β-catenin signaling pathway/methylprednisolone分类
医药卫生引用本文复制引用
郑鑫,纵加强,王佳新,陈旭昕,韩志海..基于Wnt/β-catenin信号通路探讨羟氯喹对烟雾吸入致肺纤维化大鼠的作用机制[J].解放军医学院学报,2023,44(12):1391-1398,1409,9.基金项目
后勤科研计划重点项目(BHJ16J011) （BHJ16J011）
