肺痹方干预肺纤维化小鼠肺泡上皮细胞线粒体途径凋亡的机制  

Mechanism of Feibi prescription on mitochondrial apoptosis of alveolar epithelial cells in mice with pulmonary fibrosis

作　　者：程雪[1] 荆焕熙 张运克[1] 方泓[2] Cheng Xue;Jing Huanxi;Zhang Yunke;Fang Hong(Henan University of Chinese Medicine,Zhengzhou 450046,Henan Province,China;Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)

机构地区：[1]河南中医药大学,河南省郑州市450046 [2]上海中医药大学附属龙华医院,上海市200032

出　　处：《中国组织工程研究》2025年第11期2334-2339,共6页Chinese Journal of Tissue Engineering Research

基　　金：河南省自然科学基金(222300420224),项目负责人:程雪。

摘　　要：背景:研究表明,线粒体介导的肺泡上皮细胞凋亡在肺纤维化发病中起着重要的作用,而肺痹方可以减轻肺纤维化,抑制肺纤维化小鼠细胞外机制转化。目的:探讨肺痹方对博来霉素致肺纤维化小鼠肺泡上皮细胞线粒体途径凋亡的机制。方法:40只C57BL/6雄性小鼠随机分为空白对照组、模型组、吡非尼酮组、肺痹方组,每组10只。除空白对照组外,其他3组腹腔注射博来霉素[7.5 mg/(kg·d)]建立肺纤维化模型,连续注射10 d。造模后第1天各药物组小鼠灌胃给药[51.43/(kg·d)]吡非尼酮或[12.86 mg/(kg·d)肺痹方],连续给药28 d。用药结束后取材,采用苏木精-伊红染色和Masson染色观察小鼠肺组织的形态学变化,ELISA法检测血清中白细胞介素1、白细胞介素6、白细胞介素17、白细胞介素37水平,Western-blot法检测肺组织中Bax、Bcl-2、Beclin-1和Caspase3表达。结果与结论:①肺组织的形态学观察显示,模型组肺泡间隔及肺泡腔有大量炎症细胞浸润,出现大片融合成团的纤维灶;吡非尼酮组肺泡间隔增厚,炎症细胞少量浸润,出现肺纤维灶;肺痹方组肺泡结构增宽,少量的炎症细胞浸润,肺泡结构几乎无明显受损,少量肺纤维灶。②与空白对照组相比,模型组小鼠血清白细胞介素1、白细胞介素6、白细胞介素17和白细胞介素37质量浓度明显升高(P<0.01),两用药组明显低于模型组(P<0.01),肺痹方组低于非尼酮组。③与空白对照组相比,模型组小鼠肺组织Bax和Caspase3蛋白表达显著升高,两用药组均低于模型组;与空白对照组相比,模型组Bcl-2和Beclin-1蛋白表达显著降低,两用药组均高于模型组。④结论:肺痹方可以减轻肺纤维化,其机制可能与下调白细胞介素1、白细胞介素6、白细胞介素17和白细胞介素37水平,以及调节线粒体凋亡Bax、Bcl-2、Beclin-1和Caspase3相关蛋白从而减少肺泡上皮细胞凋亡有关。BACKGROUND:Studies have shown that mitochondrial apoptosis of alveolar epithelial cells plays an important role in the pathogenesis of pulmonary fibrosis,and Feibi prescription can attenuate pulmonary fibrosis and inhibit the transformation of extracellular mechanisms in mice with pulmonary fibrosis.OBJECTIVE:To investigate the mechanism of Feibi prescription on mitochondrial apoptpsis of alveolar epithelial cells in bleomycin induced pulmonary fibrosis mice.METHODS:Forty male C57BL/6 mice were randomly divided into blank control group,model group,pirfenidone group,and Feibi prescription group.There were 10 mice in each group.Except for the blank control group,the other three groups were intraperitoneally injected with bleomycin(7.5 mg/kg per day)for 10 continuous days to establish the model of pulmonary fibrosis.On day 1 after modeling,the mice in corresponding drug groups were intragastrically administered with pirfenidone(51.43 mg/kg per day)or Feibi prescription(12.86 mg/kg per day).Drug administration lasted for 28 days.Then,morphological changes of lung tissue in mice were observed by hematoxylin-eosin staining and Masson staining.The levels of interleukin-1,interleukin-6,interleukin-17,and interleukin-37 in the serum were detected by ELISA,and the expression of Bax,Bcl-2,Beclin-1,and Caspase3 in the lung tissue was detected by western blot assay.RESULTS AND CONCLUSION:Morphological observation of lung tissue showed that in the model group,the alveolar septum and alveolar lumen were infiltrated with a large number of inflammatory cells,and there were large clusters of fibrous foci;in the pirfenidone group,alveolar septa were thickened,with a small infiltration of inflammatory cells and the appearance of pulmonary fibrous foci;in the Feibi prescription group,the alveolar structure was widened,with a small amount of inflammatory cell infiltration,and the alveolar structure was almost not obviously damaged,with a small number of lung fibrous foci.Compared with the blank control group,the mass concentrations of

关 键 词：肺痹方 肺纤维化 线粒体 博来霉素 C57BL/6小鼠 

分 类 号：R496[医药卫生—康复医学] R318[医药卫生—临床医学] R446