利那洛肽联合普芦卡必利对IBS-C小鼠的肠黏膜屏障功能及肠道免疫的影响机制OA
The mechanism of linagliptin and prucabide to influence intestinal mucosal barrier function and intestinal immunity in IBS-C mice
目的 探讨利那洛肽联合普芦卡必利对便秘型肠易激综合征(IBS-C)小鼠肠黏膜屏障功能及肠道免疫的影响机制.方法 将50 只C57BL/6 野生型小鼠随机均分为正常组、模型组、利那洛肽组、普芦卡必利组、两药联合组.干预前,除正常组外,其他各组给予冰水灌胃制备IBS-C模型小鼠.各组干预 14 天后,检测各组粪便数量及含水量、胃残留率、肠道推进率.HE染色观察各组结肠组织形态;ELISA法检测各组血清二胺氧化酶(DAO)、D-乳酸(D-LA)及内毒素(ET)水平;qRT-PCR法检测结肠组织中白细胞介素(IL)-10、γ干扰素(IFN-γ)、IL-17 及免疫球蛋白(Ig)A、IgM、IgG mRNA表达水平;Western blotting及qRT-PCR检测结肠组织Toll样受体4(TLR4)、核因子-κB p65(NF-κB p65)蛋白及其mRNA表达水平.结果 与正常组比较,模型组粪便粒数、粪便含水量、肠道推进率均降低,胃残留率及血清DAO、D-LA、ET含量升高(P<0.05);IFN-γ、IL-17、IgA、IgG mRNA和TLR4、NF-κBp65 蛋白及其mRNA表达上调,IL-10 mRNA表达下调(P<0.05).模型组结肠黏膜出现少量炎症细胞浸润.利那洛肽组、普芦卡必利组、两药联合组均能逆转上述指标变化(P<0.05),且两药联合组在各项指标上的改善程度均优于单药组(P<0.05),同时结肠炎症细胞浸润减少.结论 利那洛肽联合普芦卡必利可能通过抑制 TLR4/NF-κB信号通路改善IBS-C小鼠肠黏膜屏障功能及肠道免疫状态.
Aim To explore the mechanism of linagliptin and prucabide to influence intestinal mucosal barrier function and intestinal immunity in irritable bowel syndrome with constipation(IBS-C)mice.Methods Fifty C57BL/6 wild-type mice were randomly divided into a normal group,a model group,a linagliptin group,a pratacrolide group,and a dual-drug combination group.Before intervention,except for the normal group,all other groups were given ice water gavage to prepare IBS-C model mice.After 14 days of intervention,the quantity and moisture content of feces,gastric residual rate,and intestinal motility were measured in each group.HE staining was used to observe the morphology of colon tissues in each group;ELISA method was used to detect the levels of serum diamine oxidase(DAO),D-lactic acid(D-LA),and endotoxin(ET)in each group;qRT-PCR was used to detect the mRNA expression levels of interleukin(IL)-10,interferon(IFN-γ),IL-17,immunoglobulin(Ig)A,IgM,and IgG in colon tissue;Western blotting and qRT-PCR were used to detect the protein and mRNA expression levels of Toll-like receptor 4(TLR4),nuclear factor kap-pa-B p65(NF-κB p65)in colon tissue.Results Compared with the normal group,the model group showed a significant decrease in fecal particle count,fecal water content,and intestinal motility,while the gastric residual rate and serum DAO,D-LA,and ET levels were significantly increased(P<0.05);The mRNA expression of IFN-γ,IL-17,IgA,IgG,and the protein and mRNA of TLR4,NF-κB p65 were significantly increased,while the mRNA expression of IL-10 was decreased(P<0.05).Histopathology showed a small amount of inflammatory cell infiltration in the colon mucosa of the model group.The linagliptin group,prucabide group,and dual-drug combination group were all able to reverse the changes in the above indicators(P<0.05),and the improvement in various indicators in the dual-drug combination group was better than those in the single drug group(P<0.05),while the infiltration of colitis cells was reduced.Conclusion The combination of linagliptin and prucabide may improve intestinal mucosal barrier function and intestinal immune status in IBS-C mice by inhibiting the TLR4/NF-κB signaling pathway.
张婉;袁婷婷;王影
衡水市第四人民医院门诊药房,河北 衡水 050041衡水市第四人民医院门诊药房,河北 衡水 050041石家庄市人民医院药学部,河北 石家庄 050000
医药卫生
利那洛肽普芦卡必利便秘型肠易激综合征肠黏膜屏障功能肠道免疫
linagliptinprucabideIBS-Cintestinal mucosal barrier functionintestinal immunity
《中南医学科学杂志》 2026 (1)
20-24,5
河北省医学科学研究课题计划项目(20221701)
评论