摘要
目的:观察玉屏风散对酪氨酸激酶2/信号转导及转录激活因子3(JAK2/STAT3)信号通路的活化抑制细胞自噬的致肺纤维化效应的调控机制,探讨玉屏风散改善特发性肺纤维化(IPF)的作用机制。方法:将斯泼累格·多雷(SD)大鼠随机分为空白组,假手术组,模型组,泼尼松组,STAT3抑制剂(索拉非尼)组,玉屏风散高、中、低剂量组。模型组及各给药组大鼠均采用一次性气管内注入博来霉素(BLM)法建立肺纤维化模型。造模第14天后开始连续灌胃给药30 d,观察治疗前后各组大鼠症状、体征,肺组织形态学,肺组织中α-平滑肌肌动蛋白(α-SMA)蛋白表达、转化生长因子-β_(1)(TGF-β_(1))含量、JAK2/STAT3通路及相关自噬指标水平的变化。结果:与模型组比较,玉屏风散高、中剂量组大鼠的一般情况和肺组织损伤状态均有不同程度的改善,肺组织中TGF-β_(1)含量显著降低,α-SMA、磷酸化酪氨酸激酶2(p-JAK2)、磷酸化信号转导及转录激活因子3(p-STAT3)、髓样细胞白血病-1(Mcl-1)、微管相关蛋白1轻链3-Ⅰ(LC3-Ⅰ)及泛素结合蛋白(p62)表达显著降低,而自噬效应蛋白(Beclin 1)、微管相关蛋白1轻链3-Ⅱ(LC3-Ⅱ)表达及LC3-Ⅱ/LC3-Ⅰ比例显著升高。结论:玉屏风散能够通过抑制JAK2/STAT3通路的活化,阻断Mcl-1与Beclin1结合,从而增强Beclinl激活细胞自噬的能力,达到改善IPF的目的。
Objective:To observe the regulatory effects of Yupingfeng Powder on pulmonary fibrosis induced by inhibition of autophagy through activation of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway,and to explore the mechanism by which Yupingfeng Powder improves idiopathic pulmonary fibrosis(IPF).Methods:Sprague Dawley(SD)rats were randomly divided into a blank group,sham-operated group,model group,prednisone group,STAT3 inhibitor(sorafenib)group,and high-,medium-,and low-dose Yupingfeng Powder groups.The pulmonary fibrosis model was established in the model group and all treatment groups by a single intratracheal injection of bleomycin(BLM).From day 14 after modeling,rats received continuous intragastric administration for 30 days.Changes in symptoms,signs,and lung tissue morphology before and after treatment were observed in each group.The expression of α-smooth muscle actin(α-SMA),the content of transforming growth factor-β_(1)(TGF-β_(1)),activation of the JAK2/STAT3 signaling pathway,and levels of autophagy-related indicators in lung tissue were measured.Results:Compared with the model group,the high-and medium-dose Yupingfeng Powder groups showed varying degrees of improvement in general condition and lung tissue injury.The content of TGF-β_(1) in lung tissue was significantly reduced.The expression levels ofα-SMA,phosphorylated Janus kinase 2(p-JAK2),phosphorylated signal transducer and activator of transcription 3(p-STAT3),myeloid cell leukemia-1(Mcl-1),microtubule-associated protein 1 light chain 3-Ⅰ(LC3-Ⅰ),and ubiquitin-binding protein(p62)were significantly decreased,whereas the expression of the autophagy effector protein Beclin 1,microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ),and the LC3-Ⅱ/LC3-Ⅰratio were significantly increased.Conclusion:Yupingfeng Powder can inhibit activation of the JAK2/STAT3 signaling pathway and block the binding of Mcl-1 to Beclin 1,thereby enhancing the ability of Beclin 1 to activate autophagy and ultimately improving IPF.
作者
吴孝政
黄高
薛蕾
陈云志
WU Xiaozheng;HUANG Gao;XUE Lei;CHEN Yunzhi(School of Basic Medicine,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China)
出处
《世界中医药》
北大核心
2025年第24期4405-4414,共10页
World Chinese Medicine
基金
国家自然科学基金项目(82160861)
贵州省基础研究(自然科学)项目(黔科合基础-ZK[2023]一般411)
贵州中医药大学学术新苗项目(贵科合学术新苗[2023]-22号)。
关键词
玉屏风散
特发性肺纤维化
肺纤维化
自噬
信号转导及转录激活因子3
酪氨酸激酶2
博来霉素
机制研究
Yupingfeng Powder
Idiopathic pulmonary fibrosis
Pulmonary fibrosis
Autophagy
Signal transducer and activator of transcription 3
Janus kinase 2
Bleomycin
Mechanism research
