基于“逆流挽舟”法探索人参败毒散对溃疡性结肠炎大鼠肠黏膜屏障的干预作用  

Based on"Reverse Flow Carrying Boat"Approach to Explore the Intervention Effect of Renshen Baidu Powder on Intestinal Mucosal Barrier Ulcerative Colitis in Rats

作　　者：熊珮宇 陈岚 陈旭 张培旭 钟春 刘兴隆[1] 贾波[1] Xiong Peiyu;Chen Lan;Chen Xu;Zhang Peixu;Zhong Chun;Liu Xinglong;Jia Bo(School of Basic Medicine,Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China)

机构地区：[1]成都中医药大学基础医学院,成都610075

出　　处：《世界科学技术-中医药现代化》2021年第7期2285-2293,共9页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委员会面上项目(82074327):逆流挽舟法调控tuft细胞促肠干细胞增殖修复溃疡性结肠炎黏膜的机制研究,负责人:贾波;四川省科技厅应用基础研究(2018JY0446):基于PD-1信号介导的PI3K-Akt通路研究术苓断下汤合榆瑞灌肠液干预IBD的分子机制,负责人:贾波。

摘　　要：目的观察人参败毒散对TNBS诱导的溃疡性结肠炎大鼠肠黏膜屏障的影响及其可能机制。方法将60只雄性SD大鼠随机分组,采用TNBS诱导法造模,人参败毒散各剂量(31.2、15.6、8 g·kg^(-1))连续7天灌胃。检测各组血清白介素-1β(Interleukin-1β,IL-1β)、白介素-6(Interleukin-6,IL-6)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、干扰素-γ(Interferon-γ,IFN-γ)含量;结肠组织咬合蛋白(Occludin)、闭合蛋白(Claudin-5)与闭锁蛋白(ZO-1)m RNA和蛋白水平。结果与空白(Control)组比较,模型(Model)组的血清IL-1β、IL-6、TNF-α、以及IFN-γ含量明显增高(P<0.05),结肠组织Occludin、Claudin-5与ZO-1m RNA和蛋白水平明显下调(P<0.05)。经治疗后,人参败毒散高、中、低剂量(RH、RM、RL)组血清中炎症因子IL-1β、IL-6、TNF-α、IFN-γ含量均有降低,RH组干预结果存在统计学意义(P<0.05);结肠组织Occludin、Claudin-5以及ZO-1 m RNA表达和蛋白表达均有上调,且RH组干预效应明显优于其他给药组,具有统计学意义(P<0.05)。结论"逆流挽舟法"代表方人参败毒散能有效改善UC大鼠症状,其作用机制可能与抑制炎性细胞因子IL-1β、IL-6、TNF-α、IFN-γ释放,上调结肠黏膜Occludin、Claudin-5与ZO-1 m RNA和蛋白表达,促进肠上皮紧密连接修复,改善肠黏膜通透性有关。Objective To observe the effect of Renshen Baidu Powder on the intestinal mucosal barrier of TNBS-induced ulcerative colitis rats and its possible mechanism.Methods Sixty male SD rats were randomly divided intogroups,modeled by TNBS induction method,and each dose of Renshen Baidu Powder(31.2,15.6,8 g·kg^(-1))wasintragastrically administered for 7 days.Serum interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)content were detected;colonic tissue occludin(Occludin),claudin(Claudin-5)andoccludin(ZO-1)m RNA and protein levels were also determined.Results Compared with the control group,the serumlevels of IL-1β,IL-6,TNF-α,and IFN-γin the model group were significantly increased(P<0.05),and the colontissue Occludin,Claudin-5 and ZO-1 m RNA and protein levels were significantly down-regulated(P<0.05).Aftertreatment,the levels of serum inflammatory factors IL-1β,IL-6,TNF-αand IFN-γin the high,medium and low dose(RH,RM,RL)groups of Renshen Baidu Powder decreased,and there was statistical significance for the results ofintervention in the RH group(P<0.05);colonic tissue Occludin,Claudin-5 and ZO-1 m RNA expression and proteinexpression were all up-regulated,and the intervention effect of the RH group was significantly better than that of otheradministration groups,with statistical significance(P<0.05).Conclusion Renshen Baidu Powder,the representative of"Reverse Flow Carrying Boat Method",can effectively improve the symptoms of UC rats,and its mechanism may berelated to inhibiting the release of inflammatory cytokines IL-1β,IL-6,TNF-α,and IFN-γColonic mucosa Occludin,Claudin-5 and ZO-1 m RNA and protein expression,promote the repair of intestinal epithelial tight junctions,andimprove the permeability of the intestinal mucosa.

关 键 词：溃疡性结肠炎 人参败毒散 黏膜屏障 紧密连接 

分 类 号：R284[医药卫生—中药学]