基于PGAM5/Drp1/PINK1/Parkin轴调控线粒体自噬探讨清解化攻方对急性胰腺炎大鼠肠黏膜屏障的保护作用  

The protective effect of Qingjie Huagong decoction on intestinal mucosalbarrier of SAP rats based on regulation of mitochondrial autophagy byPGAM5/Drp1/PINK1/Parkin axis

作　　者：朱晓东 刘锟荣 冯敏超 班莹 唐曦平 陈国忠[2] ZHU Xiao-dong;LIU Kun-rong;FENG Min-chao;BAN Ying;TANG Xi-ping;CHEN Guo-zhong(Graduate School,Guangxi University of Chinese Medicine,Nanning 530200,China;Dept of Gastroenterology,the First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,China;Dept of General Internal Medicine,Affiliated Cancer Hospital of Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西中医药大学研究生院,广西南宁530200 [2]广西中医药大学第一附属医院脾胃病科,广西南宁530023 [3]广西医科大学附属肿瘤医院综合内科,广西南宁530021

出　　处：《中国药理学通报》2025年第3期561-567,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82160890);广西省自然科学基金资助项目(No 2024GXNSFAA010246,2020GXNSFAA297062);国家中医优势专科建设项目(No 2024010)。

摘　　要：目的探究清解化攻方对重症急性胰腺炎(severe acute pancreatitis,SAP)大鼠肠黏膜屏障保护作用的机制。方法构建SAP大鼠模型,设立假手术组、模型组、不同剂量清解化攻方给药组和阳性对照组。HE染色观察组织病理学变化;ELISA法检测大鼠血清二胺氧化酶(diamine oxidase,DAO)、D-乳酸(D-lactic acid,D-LA)水平;透射电镜观察回肠组织线粒体情况;qRT-PCR、Western blot分别检测大鼠回肠组织中PGAM5、Drp1、PINK1、Parkin、LC3B mRNA和蛋白的表达。结果与假手术组相比,模型组大鼠胰腺和回肠组织出现明显病理改变,回肠组织线粒体结构异常、自噬小体数量减少;血清中DAO、D-LA含量上升(P<0.01);回肠组织中PGAM5、Drp1、PINK1、Parkin、LC3B mRNA和蛋白表达明显下降。与模型组相比,乌司他丁和清解化攻方各剂量组中的胰腺和回肠病理改善,回肠线粒体损伤减轻,自噬小体数量增多;血清中DAO、D-LA含量均有降低;回肠组织中PGAM5、Drp1、PINK1、Parkin、LC3B mRNA和蛋白表达明显上升。结论清解化攻方可能通过调控PGAM5/Drp1/PINK1/Parkin轴以提升肠上皮细胞线粒体自噬水平,从而改善肠上皮细胞的修复水平,发挥保护SAP肠黏膜屏障的效应。Aim To investigate the mechanism of intestinal mucosal barrier protective effect of Qingjie Huagong decoction(QJHGD)on rats with severe acute pancreatitis(SAP).Methods The SAP rat model was constructed,and the sham-operation group,the model group,the group administered with different dosages of QJHGD,and the positive control group were set up respectively.HE staining was used to observe the histopathological changes.ELISA was employed to detect the serum levels of diamine oxidase(DAO)and D-lactic acid(D-LA)in rats.Transmission electron microscopy was utilized to observe the mitochondria of ileal tissues.qRT-PCR and Western blot were applied to detect the mRNA and protein expression of PGAM5,Drp1,PINK1,Parkin,LC3B in ileal tissues of rats.Results Compared with the sham-operated group,the pancreas and ileum tissues of rats in the model group showed obvious pathological changes,with abnormal mitochondrial structure and reduced number of autophagic vesicles in the ileum tissues.The levels of DAO and D-LA in serum increased(P<0.01),and the mRNA and protein expression of PGAM5,Drp1,PINK1,Parkin,and LC3B in the ileum tissues decreased significantly.Compared with the model group,pancreatic and ileal pathology were improved,mitochondrial damage in the ileum was reduced,and the number of autophagic vesicles increased in the QJHGD group.The serum levels of DAO and D-LA were reduced,and the expression of PGAM5,Drp1,PINK1,Parkin,and LC3B mRNA and protein in the ileal tissues increased significantly.Conclusions QJHGD may exert a protective effect on the SAP intestinal mucosal barrier by regulating the PGAM5/Drp1/PINK1/Parkin axis in order to elevate the level of mitochondrial autophagy in the intestinal epithelial cells,thereby improving the level of repair of the intestinal epithelial cells.

关 键 词：清解化攻方 PGAM5/Drp1/PINK1/Parkin轴 线粒体自噬 重症急性胰腺炎 肠黏膜屏障 保护作用 

分 类 号：R-332[医药卫生] R289.5R322.45R329.24R392R576.1