| 张婉,袁婷婷,王影.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.[J].中南医学科学杂志.,2026,(1):20-24. |
| 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 |
| The mechanism of linagliptin and prucabide to influence intestinal mucosal barrier function and intestinal immunity in IBS-C mice |
| 投稿时间：2025-05-24 修订日期：2025-08-28 |
| DOI：10.15972/j.cnki.43-1509/r.2026.01.004 |
| 中文关键词: 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 |
| 英文关键词:linagliptin prucabide IBS-C intestinal mucosal barrier function intestinal immunity |
| 基金项目:河北省医学科学研究课题计划项目(20221701) 作者简介:张婉,主管药师,研究方向为临床药学,E-mail为yuanyuanfangc@163.com。通信作者王影,硕士,主管药师,研究方向为临床药学,E-mail为121829629@qq.com。 |
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| 中文摘要: |
| 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-κB p65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。 |
| 英文摘要: |
| AimTo 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. MethodsFifty 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 kappa-B p65 (NF-κB p65) in colon tissue. ResultsCompared 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. ConclusionThe 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. |
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