苦参碱对肺间质纤维化JAKs/STATs通路的影响  

Effects of matrine on JAK-STAT signaling transduction pathway in bleomycin-induced pulmonary fibrosis

作　　者：马秀琴[1] 陈如华[1] 刘秀芳[1] 谢婧[1] 史可云[1] 端礼荣[2] 

机构地区：[1]宜兴市人民医院呼吸内科,江苏宜兴214200 [2]江苏大学医学院,江苏镇江212001

出　　处：《中国医院药学杂志》2014年第8期629-633,共5页Chinese Journal of Hospital Pharmacy

基　　金：江苏大学2010年度临床医学科技发展基金资助(编号:JLY2010033)

摘　　要：目的:观察苦参碱(Matrine,Mat)在博来霉素(BLM)诱导的小鼠肺组织纤维化中对JAK-STAT通路的影响,并探讨其抗纤维化作用的机制。方法:120只雄性C57BL/6小鼠随机分为对照组、模型组和治疗组,采用气管内灌注博来霉素的方法建立小鼠肺纤维化模型,治疗组给予每日一次苦参碱灌胃,分别于给药后第3,7,14,21,28天每组分别处死8只小鼠。取肺组织进行HE染色,并用免疫组化和RT-PCR技术检测肺组织中JAK、STAT1、STAT3的表达。分离培养肺成纤维细胞并观察苦参碱对肺纤维化细胞的抑制情况。结果:治疗组的肺泡炎和肺纤维化程度明显轻于模型组(P<0.05),模型组JAK,STAT1,STAT3蛋白和mRNA的表达高于对照组,治疗组JAK,STAT1,STAT3蛋白和mRNA的表达较模型组明显减少(P<0.05),苦参碱治疗对肺纤维化细胞有明显抑制作用(P<0.05)。结论:肺间质纤维化可引起JAK、STAT1、STAT3的大量表达,苦参碱通过抑制JAK-STAT1和JAK-STAT3信号传导通路发挥抗肺纤维化作用。OBJECTIVE To study the effects of matrine on JAK-STAT signaling transduction pathway in bleomycin-induced pulmonary fibrosis in mice and its possible mechanism. METHODS One hundred and twenty male C57BL/6 mice were ran- domly divided into three groups：control group, model group and treatment group. Pulmonary fibrosis model was established by intratracheal instillation of bleomycin（gLM）. Then the mice were given with matrine by the gastric lavage in treatment group every day. Eight mice in each group were sacrificed at 3, 7, 14, 21and 28 days. Histological changes of the lungs were evalua- ted by HE staining. Immuno histochemistry staining and RT-PCR were used to examine the expression of JAK, STAT1, STAT3 in lung tissue~ Human lung fibroblasts （LFs） MRC-5 were cultured and the inhibitory effect of matrine on LFs was observed using an enzyme immunoassay instrument. RESULTS Alveolitis and pulmonary fibrosis in treatment group decreased significantly after treatment with matrine and was improved compared with the model group （P〈0. 05）. The expression of JAK, STAT1, and STAT3 in the treatment group significantly decreased compared with that in the model group. The RT- PCR demonstrated that the mRNA expression of JAK, STAT1, and STAT3 in the lung tissues of the model group was signifi- cantly higher than that in the control group, whereas their mRNA expression in the treatment group was noticeably lower than that in the model group （P〈0. 05）. Matrine had a significant inhibitory effect on LFs compared with model group. CONCLU- SION The pulmonary interstitial fibrosis may induce significant increase of JAK, STATI, STAT3 expressions in lung tissue. Matrine can inhibit the pulmonary fibrosis by inhibition of JAK-STAT signaling transduction pathway.

关 键 词：肺纤维化 博来霉素 苦参碱 信号传导通路 

分 类 号：R965[医药卫生—药理学]