基于JNK/P38/NF-κB信号通路探讨清解化攻方改善重症急性胰腺炎诱导的急性肺损伤的作用机制  

Investigating the mechanism of Qingjie Huagong Decoction in attenuating acute lung injury induced by severe acute pancreatitis via the JNK/P38/NF-κB signaling pathway

作　　者：李凯 冯敏超 朱晓东 班莹 刘锟荣 禤传凤 唐曦平 陈国忠[2] LI Kai;FENG Min-cha;ZHU Xiao-dong;BAN Yin;LIU Kun-rong;XUAN Chuan-feng;TANG Xi-ping;CHEN Guo-zhong(First Clinical School of Guangxi University of Chinese Medicine,Nanning 530200,China;First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530001,China;Second Clinical Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510006,China;Guangxi Key Laboratory of Molecular Biology of Traditional Chinese Medicine and Preventive Medicine,Nanning 530001,China;Affiliated Cancer Hospital of Guangxi Medical University,Nanning 530001,China)

机构地区：[1]广西中医药大学第一临床医学院,广西南宁530200 [2]广西中医药大学第一附属医院,广西南宁530001 [3]广州中医药大学第二临床医学院,广东广州510006 [4]广西中医药防治医学分子生物重点实验室,广西南宁530001 [5]广西医科大学附属肿瘤医院,广西南宁530021

出　　处：《时珍国医国药》2025年第5期807-813,共7页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(82160890);国家中医优势专科建设项目(2024010);广西自然科学基金面上项目(2024GXNSFAA010246,2020GXNSFAA297062);广西中医药大学第一附属医院院级科研项目(2020QN024);中医药地方标准项目(2024001-02-05);广西中医药大学博士科研启动基金项目(2022BS029)。

摘　　要：目的研究清解化攻方通过调控JNK/P38/NF-κB信号通路,干预重症急性胰腺炎急性肺损伤炎症反应,调节细胞凋亡的潜在分子机制。方法将36只SPF级雄性大鼠随机分为假手术组、模型组、西药组、清解化攻方低、中、高剂量组,每组6只。取实验大鼠组织及血液,通过HE染色、ELISA、IHC、RT-PCR、Western blot等多重检验探讨调控JNK/P38/NF-κB信号通路对重症急性胰腺炎诱导的急性肺损伤影响的分子机制。结果与假手术组相比较,肺组织呈多纤维样不规则排列重叠;胰腺小叶间隔增大,腺泡萎缩,存在炎性细胞浸润现象,病理评分升高,脂肪酶、淀粉酶、IL-1β、TNF-α、IL-6浓度水平明显上升(P<0.05),JNK、P38、NF-κB、AP1 mRNA和蛋白表达水平上调(P<0.05);与模型组相比,清解化攻方各剂量组与西药组均可减轻胰腺及肺组织病理损伤,可降低该模型肺组织中脂肪酶、淀粉酶、IL-1β、TNF-α、IL-6的含量(P<0.05),下调JNK、P38、NF-κB、AP1 mRNA和蛋白表达水平(P<0.05)。结论清解化攻方可能通过降低IL-1β、TNF-α、IL-6等炎症因子的表达,抑制JNK/P38/NF-κB信号通路,降低凋亡基因的活化,改善细胞凋亡,从而达到保护胰腺和肺组织,可作为临床补充治疗手段。Objective To investigate the potential molecular mechanism by which Qingjie Huagong Decoction(QJHGD)alleviates inflammation and regulates apoptosis in acute lung injury(ALI)induced by severe acute pancreatitis(SAP)through the JNK/P38/NF-κB signaling pathway.Methods Thirty-six SPF-grade male rats were randomly assigned to the sham-operated group,the model group,the Western medicine group,and the QJHGD low-,medium-,and high-dose groups(n=6 per group).Tissue and blood samples were collected from the experimental rats.The molecular mechanisms involving the JNK/P38/NF-κB signaling pathway were explored using hematoxylin-eosin(HE)staining,ELISA,IHC,RT-PCR,and Western blot(WB)analysis.Results Compared with the sham-operated group,the model group exhibited irregularly arranged and overlapping fibrotic structures in the lung tissue,enlarged pancreatic interlobular septa,acinar atrophy,and inflammatory cell infiltration.Pathological scores,as well as the concentrations of lipase,amylase,IL-1β,TNF-α,and IL-6,were significantly elevated(P<0.05).The expression levels of JNK,P38,NF-κB,and AP1 mRNA and protein were also up-regulated(P<0.05).Compared with the model group,the Western medicine group and QJHGD groups with different doses showed reduced pathological damage in pancreatic and lung tissues,decreased concentrations of lipase,amylase,IL-1β,TNF-α,and IL-6 in the lung tissues(P<0.05),and down-regulated expression levels of JNK,P38,NF-κB,and AP1 mRNA and protein(P<0.05).Conclusion QJHGD may exert protective effects on pancreatic and lung tissues by down-regulating inflammatory factors such as IL-1β,TNF-α,and IL-6,inhibiting the JNK/P38/NF-κB signaling pathway,and reducing apoptotic gene activation,thus mitigating apoptosis.QJHGD may serve as a potential complementary treatment for SAP-induced ALI.

关 键 词：JNK/P38/NF-κB通路 清解化攻方 重症急性胰腺炎 急性肺损伤 炎症反应 细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]