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TRPV1 参与蜂胶对溃疡性结肠炎结肠组织的保护作用。

TRPV1 participates in the protective effect of propolis on colonic tissue of ulcerative colitis.

机构信息

Department of Physiology, School of Basic Medical Sciences, Wannan Medical College, Wuhu Anhui 241002.

Clinical Medical School, Wannan Medical College, Wuhu Anhui 241002.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Feb 28;48(2):182-190. doi: 10.11817/j.issn.1672-7347.2023.220426.

Abstract

OBJECTIVES

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) mainly characterized by inflammation, ulceration and erosion of colonic mucosa and submucosa. Transient receptor potential vanilloid 1 (TRPV1) is an important mediator of visceral pain and inflammatory bowel disease. This study aims to investigate the protective effect of water soluble propolis (WSP) on UC colon inflammatory tissue and the role of TRPV1.

METHODS

Male SD rats were randomly divided into 6 groups (=8): a normal control (NC) group, an ulcerative colitis model (UC) group, a low-WSP (L-WSP) group, a medium-WSP (M-WSP) group, a high-WSP (H-WSP) group, and a salazosulfapyridine (SASP) group. The rats in the NC group drank water freely, and the other groups drank 4% dextran sulfate sodium (DSS) solution freely for 7 d to replicate the ulcerative colitis model. Based on the successful replication of the UC, the L-WSP, M-WSP, and H-WSP groups were given 50, 100, and 200 mg/kg of water-soluble propolis by gavage for 7 d, and the SASP group was given 100 mg/kg of sulfasalazine by gavage for 7 d. The body weight of rats in each group was measured at the same time every day, the fecal traits and occult blood were observed to record the disease activity index (DAI). After intragastric administration, the animals were sacrificed after fasted 24 h. Serum and colonic tissue were collected, and the changes of MDA, IL-6 and TNF-α were detected. The pathological changes of colon tissues were observed by HE staining, and the expression of TRPV1 in colon tissues was observed by Western blotting, immunohistochemistry, and immunofluorescence.

RESULTS

The animals in each group that drank DSS freely showed symptoms such as weight loss, decreased appetite, depressed state, and hematochezia, indicating that the model was successfully established. Compared with the NC group, DAI scores of other groups were increased (all <0.05). MDA, IL-6, TNF-α in serum and colon tissues of the UC group were increased compared with the NC group (all <0.01), and they were decreased after WSP and SASP treatment (all <0.01). The results of showed that the colon tissue structure was obviously broken and inflammatory infiltration in the UC group, while the H-WSP group and the SASP group significantly improved the colon tissue and alleviated inflammatory infiltration. The expression of TRPV1 in colon tissues in the UC group was increased compared with the NC group (all <0.01), and it was decreased after WSP and SASP treatment.

CONCLUSIONS

WSP can alleviate the inflammatory state of ulcerative colitis induced by DSS, which might be related to the inhibition of inflammatory factors release, and down-regulation or desensitization of TRPV1.

摘要

目的

溃疡性结肠炎(UC)是一种主要以结肠黏膜和黏膜下层炎症、溃疡和糜烂为特征的炎症性肠病(IBD)。瞬时受体电位香草醛 1(TRPV1)是内脏疼痛和炎症性肠病的重要介质。本研究旨在探讨水不溶性蜂胶(WSP)对 UC 结肠炎症组织的保护作用及其与 TRPV1 的关系。

方法

雄性 SD 大鼠随机分为 6 组(n=8):正常对照组(NC)、溃疡性结肠炎模型组(UC)、低 WSP(L-WSP)组、中 WSP(M-WSP)组、高 WSP(H-WSP)组、柳氮磺胺吡啶(SASP)组。NC 组自由饮水,其余各组自由饮用 4%葡聚糖硫酸钠(DSS)溶液 7 d 复制溃疡性结肠炎模型。在 UC 成功复制的基础上,L-WSP、M-WSP 和 H-WSP 组分别灌胃 50、100 和 200 mg/kg 水不溶性蜂胶 7 d,SASP 组灌胃 100 mg/kg 柳氮磺胺吡啶 7 d。每天同时测量各组大鼠体重,观察粪便特征和隐血,记录疾病活动指数(DAI)。灌胃后禁食 24 h 处死动物,收集血清和结肠组织,检测 MDA、IL-6 和 TNF-α的变化。HE 染色观察结肠组织病理变化,Western blot、免疫组化和免疫荧光法观察结肠组织 TRPV1 的表达。

结果

各组自由饮用 DSS 的动物均出现体重减轻、食欲下降、精神萎靡、血便等症状,表明模型建立成功。与 NC 组相比,其他各组的 DAI 评分均升高(均<0.05)。与 NC 组相比,UC 组血清和结肠组织中 MDA、IL-6、TNF-α均升高(均<0.01),WSP 和 SASP 治疗后均降低(均<0.01)。UC 组结肠组织结构明显破坏,炎症浸润明显,H-WSP 组和 SASP 组明显改善结肠组织,减轻炎症浸润。与 NC 组相比,UC 组结肠组织 TRPV1 表达增加(均<0.01),WSP 和 SASP 治疗后表达降低。

结论

WSP 可减轻 DSS 诱导的溃疡性结肠炎的炎症状态,可能与抑制炎症因子释放、下调或脱敏 TRPV1 有关。

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