MyD88抑制剂对急性胰腺炎相关性胃损伤的保护作用及机制研究  

Protective Effect and Mechanism of MyD88 Inhibitor in Acute Pancreatitis Associated Gastric Injury

作　　者：王豪 刘键桦 游建[1] Wang Hao;Liu Jianhua;You Jian(Department of General Surgery,Wuhan Fourth Hospital,Wuhan 430030,China;General Surgery Department,Hubei Cancer Hospital,Wuhan 430079,China)

机构地区：[1]武汉市第四医院普通外科胃肠外科,武汉430030 [2]湖北省肿瘤医院普通外科,武汉430079

出　　处：《华中科技大学学报(医学版)》2025年第2期198-202,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：吴阶平医学基金会临床科研专项基金资助(No.320.6750.2023-11-8)。

摘　　要：目的探讨MyD88抑制剂St-2825在治疗牛磺胆酸钠诱导的急性胰腺炎相关性胃损伤中对炎症通路的抑制作用,及其对胃组织的保护功效。方法大鼠胰腺包膜下注射牛磺胆酸钠,建立急性胰腺炎模型。大鼠随机分为正常对照组(C组,接受生理盐水处理)、急性胰腺炎组(P组,接受牛磺胆酸钠+生理盐水处理)和干预组(T组,接受牛磺胆酸钠+MyD88抑制剂St-2825处理),每组16只,共计48只。建模2 h及6 h后,获取大鼠胰腺及胃组织样本。样本经石蜡包埋并切片,经苏木精-伊红(HE)染色,比较各组组织病理评分。ELISA测定各组大鼠血清中肿瘤坏死因子-α(TNF-α)、白细胞介素1(IL-1)和白细胞介素6(IL-6)的蛋白表达。免疫荧光染色技术检测各组大鼠胃组织中免疫细胞浸润。免疫印迹法检测各组大鼠胃组织TLR/MyD88/NF-κB p65通路蛋白中MyD88的蛋白表达及p65磷酸化水平。结果在牛磺胆酸钠诱导的急性胰腺炎相关性胃损伤中,大鼠胰腺及胃部病理评分随时间升高;血浆中TNF-α、IL-1和IL-6水平显著上升;胰腺损伤期间,胃组织内中性粒细胞、巨噬细胞、树突状细胞及T淋巴细胞浸润数量显著增加。组织内上调的MyD88可激活NF-κB通路,p65磷酸化入核,驱动下游炎症因子的转录;MyD88抑制剂St-2825的干预可阻止p65磷酸化入核,降低下游炎症反应并减少胃组织内免疫细胞的浸润。结论在胰腺损伤期间,胃组织伴随进行性受损;MyD88抑制剂St-2825则能够降低急性胰腺炎相关性胃组织内的炎症反应,减少免疫细胞浸润,对急性胰腺炎相关性胃损伤起到一定的保护作用。Objective To investigate the inhibitory effect of MyD88 inhibitor St-2825 on inflammatory pathways and its protective efficacy on gastric tissue in sodium taurocholate-induced acute pancreatitis-associated gastric injury.Methods An acute pancreatitis rat model was established by subcapsular pancreatic injection of sodium taurocholate.Rats were randomly divided into normal control group(Group C,received saline+saline treatment),acute pancreatitis group(Group P,received sodium taurocholate+saline treatment),and intervention group(Group T,received sodium taurocholate+MyD88 inhibitor St-2825 treatment),with 16 rats in each group,48 rats in total.Pancreatic and gastric tissue samples were collected at 2 h and 6 h post-modeling.The samples were paraffin-embedded,sectioned,and stained with hematoxylin-eosin(HE)for comparative pathological scoring.Serum levels of tumor necrosis factor-α(TNF-α),interleukin-1(IL-1),and interleukin-6(IL-6)were measured by ELISA.Immunofluorescence staining was performed to assess immune cell infiltration in gastric tissues.Western blot was used to determine the protein expression of MyD88 and the phosphorylation ratio of p65 in the TLR/MyD88/NF-κB p65 signaling pathway in rat gastric tissues.Results In sodium taurocholate-induced acute pancreatitis-associated gastric injury rats,both pancreatic and gastric pathological scores were increased progressively over time.The plasma levels of TNF-α,IL-1 and IL-6 were significantly elevated.During pancreatic injury,gastric tissues exhibited markedly increased infiltration of neutrophils,macrophages,dendritic cells and T lymphocytes.The upregulated MyD88 in tissues stimulated NF-κB pathway activation,leading to phosphorylated p65 nuclear translocation and downstream inflammatory factors transcription.MyD88 inhibitor St-2825 intervention effectively blocked p65 phosphorylation and nuclear translocation,attenuated downstream inflammatory responses,and reduced immune cell infiltration in gastric tissues.Conclusion Gastric tissues undergo progressive

关 键 词：MyD88抑制剂 急性胰腺炎相关性胃损伤 p65磷酸化 炎症因子 

分 类 号：R576[医药卫生—消化系统]