清解化攻方调控Opa1、Mfn1、Drp1、Fis1维持线粒体动力学平衡改善急性胰腺炎大鼠胰腺损伤的作用机制  

Mechanism of Qingjie Huagong Decoction Regulating Opa1,Mfn1,Drp1 and Fis1 to Maintain Mitochondrial Dynamics Balance and Improve Pancreatic Injury in Rats with Acute Pancreatitis

作　　者：朱晓东 刘锟荣 班莹 冯敏超 苏攀[2] 禤传凤 唐曦平 陈国忠[2,4] ZHU Xiaodong;LIU Kunrong;BAN Ying;FENG Minchao;SU Pan;XUAN Chuanfeng;TANG Xiping;CHEN Guozhong(Guangxi University of Chinese Medicine,Nanning 530200 Guangxi,China;The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine,Nanning 530023 Guangxi,China;Guangxi Medical University Affiliated Cancer Hospital,Nanning 530021 Guangxi,China;Guangxi Key Laboratory of Molecular Biology for the Prevention and Treatment of Chinese Medicine,Nanning 530023 Guangxi,China)

机构地区：[1]广西中医药大学,广西南宁530200 [2]广西中医药大学第一附属医院,广西南宁530023 [3]广西医科大学附属肿瘤医院,广西南宁530021 [4]广西中医药防治医学分子生物重点实验室,广西南宁530023

出　　处：《中药新药与临床药理》2025年第3期368-375,共8页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金项目(82160890);广西自然科学基金面上项目(2024GXNSFAA010246);国家中医优势专科建设项目(2024010);2022年广西中医药大学引进博士科研启动基金项目(2022BS029);“十四五”防城港市科技计划项目(防科AB23006034)。

摘　　要：目的观察清解化攻方对急性胰腺炎大鼠胰腺损伤及线粒体动力学相关蛋白的影响,探讨其治疗急性胰腺炎的潜在作用机制。方法采用腹腔注射雨蛙素方法建立急性胰腺炎大鼠模型,分别设置空白组、模型组、不同剂量清解化攻方给药组和乌司他丁组,不同剂量清解化攻方组予以低、中、高剂量中药灌胃,乌司他丁组予以乌司他丁干预,空白组和模型组予以等比例生理盐水灌胃;HE染色观察胰腺组织病理形态学变化;ELISA法检测大鼠血清α-AMS、PNLP、IL-1β、IL-6、IL-8和TNF-α含量;Western Blot法检测大鼠胰腺组织线粒体动力学相关蛋白Opa1、Mfn1、Drp1、Fis1表达水平;qRT-PCR法检测大鼠胰腺组织线粒体动力学相关Opa1、Mfn1、Drp1、Fis1 mRNA转录水平。结果与空白组比较,模型组大鼠胰腺细胞弥漫性出血坏死、小叶间隔水肿明显,见炎性细胞浸润,血清中α-AMS、PNLP、IL-1β、IL-6、IL-8和TNF-α含量明显升高(P<0.01),胰腺组织中Drp1、Fis1蛋白及mRNA表达水平明显上升(P<0.01),Opa1、Mfn1蛋白及mRNA表达水平明显下降(P<0.01);与模型组比较,清解化攻方各剂量组和乌司他丁组均可改善胰腺组织病理学,降低血清中α-AMS、PNLP、IL-1β、IL-6、IL-8和TNF-α表达水平(P<0.05,P<0.01),降低胰腺组织中Drp1、Fis1蛋白及mRNA表达水平(P<0.01),升高Opa1、Mfn1蛋白及mRNA表达水平(P<0.01)。结论清解化攻方可能通过调控线粒体动力学相关蛋白的平衡,改善胰腺损伤和炎症反应,从而起到保护胰腺组织的作用。Objective To observe the effects of Qingjie Huagong Decoction on pancreatic injury and mitochondrial dynamics-related proteins in rats with acute pancreatitis(AP),and to explore the possible mechanism in the treatment of AP.Methods The rat model of acute pancreatitis was established by intraperitoneal injection of Cerulein.The blank group,model group,different doses of Qingjie Huagong Decoction group and Ulinastatin group were set up respectively.Different doses of Qingjie Huagong Decoction group were given low-,medium-and high-doses of traditional Chinese medicine by gavage.Ulinastatin group was given Ulinastatin intervention,blank group and model group were given equal proportion of normal saline by gavage.HE staining was used to observe the pathological changes of pancreatic tissue.The serum levels ofα-AMS,PNLP,IL-1β,IL-6,IL-8 and TNF-α were detected by ELISA.The expression levels of mitochondrial dynamics-related proteins Opa1,Mfn1,Drp1 and Fis1 in rat pancreatic tissue were detected by Western Blot.The mRNA transcription levels of Opa1,Mfn1,Drp1 and Fis1 related to mitochondrial dynamics in rat pancreatic tissue were detected by qRT-PCR.Results Compared with the blank group,the rats in the model group had diffuse hemorrhage and necrosis of pancreatic cells,obvious edema of interlobular septum,and inflammatory cell infiltration.The levels ofα-AMS,PNLP,IL-1β,IL-6,IL-8 and TNF-α in serum were significantly increased(P<0.01).The protein and mRNA expression levels of Drp1 and Fis1 in pancreatic tissue were significantly increased(P<0.01),and the protein and mRNA expression levels of Opa1 and Mfn1 were significantly decreased(P<0.01).Compared with the model group,the pathology of pancreatic tissue was improved,the expression levels ofα-AMS,PNLP,IL-1β,IL-6,IL-8 and TNF-α in serum were decreased(P<0.01),the protein and mRNA expression levels of Drp1 and Fis1 in pancreatic tissue were decreased(P<0.01),and the protein and mRNA expression levels of Opa1 and Mfn1 were increased(P<0.05),in each dose group of Qi

关 键 词：急性胰腺炎 清解化攻方 线粒体动力学 线粒体分裂 线粒体融合 大鼠 

分 类 号：R285.5[医药卫生—中药学]