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补中益气颗粒通过TLR4/NF-κB/MLCK信号通路增强溃疡性结肠炎大鼠结肠紧密连接的完整性。

Bu-Zhong-Yi-Qi Granule Enhances Colonic Tight Junction Integrity via TLR4/NF-B/MLCK Signaling Pathway in Ulcerative Colitis Rats.

作者信息

Kang Xiuhong, Jia Mengdi, Zhao Luqing, Zhang Shengsheng

机构信息

Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China.

出版信息

Evid Based Complement Alternat Med. 2021 Mar 9;2021:6657141. doi: 10.1155/2021/6657141. eCollection 2021.

DOI:10.1155/2021/6657141
PMID:33763148
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7963908/
Abstract

BACKGROUND

Bu-zhong-yi-qi granule (BZYQ), a sort of Chinese herbal medicine, has exhibited therapeutic effects on ulcerative colitis (UC). However, the mechanism of BZYQ has not been fully clarified. This study was aimed at investigating the effects of BZYQ on UC rats model and at exploring its potential mechanism.

METHODS

The UC rats were established by enema of trinitrobenzene sulfonic acid (TNBS). The therapeutic effects of BZYQ treatment were evaluated by disease activity index (DAI), colon macroscopic damage index (CMDI) scores, and histological observation. The mRNA levels of tumor necrosis factor- (TNF-), interleukin-1 (IL-1), and interleukin-10 (IL-10) were measured by quantitative real time-polymerase chain reaction (qPCR). The expression of tight junction (TJ) proteins, occludin and claudin-1, in the colon was determined by Western blot and immunofluorescence. The expression of toll-like receptors 4 (TLR4), nuclear factor-kappa B (NF-B), p-NF-B, myosin light chain kinase (MLCK), MLC, and p-MLC levels in colon was determined by Western blot or qPCR.

RESULTS

The results showed that BZYQ could attenuate DAI, CMDI, and histological inflammation. TJ proteins expression was decreased in UC rats, but treatment with BZYQ restored the expression of occludin and claudin-1. In addition, BZYQ administration ameliorated UC-associated increase in the production of TNF-, IL-1, and the expression of TLR4, NF-B, p-NF-B, MLCK, MLC, and p-MLC, while BZYQ administration increased the production of IL-10.

CONCLUSIONS

The therapeutic effect of BZYQ on UC is at least partially through regulation of the secretion of some inflammatory cytokines and improvement of TJ integrity via TLR4/NF-B/MLCK pathway.

摘要

背景

补中益气颗粒(BZYQ)是一种中药,已显示出对溃疡性结肠炎(UC)的治疗作用。然而,BZYQ的作用机制尚未完全阐明。本研究旨在探讨BZYQ对UC大鼠模型的影响并探索其潜在机制。

方法

通过三硝基苯磺酸(TNBS)灌肠建立UC大鼠模型。通过疾病活动指数(DAI)、结肠宏观损伤指数(CMDI)评分和组织学观察评估BZYQ治疗的效果。通过定量实时聚合酶链反应(qPCR)测量肿瘤坏死因子-(TNF-)、白细胞介素-1(IL-1)和白细胞介素-10(IL-10)的mRNA水平。通过蛋白质免疫印迹法和免疫荧光法测定结肠中紧密连接(TJ)蛋白occludin和claudin-1的表达。通过蛋白质免疫印迹法或qPCR测定结肠中Toll样受体4(TLR4)、核因子-κB(NF-κB)、p-NF-κB、肌球蛋白轻链激酶(MLCK)、MLC和p-MLC的水平。

结果

结果表明,BZYQ可减轻DAI、CMDI和组织学炎症。UC大鼠中TJ蛋白表达降低,但BZYQ治疗可恢复occludin和claudin-1的表达。此外,BZYQ给药改善了UC相关的TNF-、IL-1产生增加以及TLR4、NF-κB、p-NF-κB、MLCK、MLC和p-MLC的表达,而BZYQ给药增加了IL-10的产生。

结论

BZYQ对UC的治疗作用至少部分是通过调节某些炎性细胞因子的分泌以及通过TLR4/NF-κB/MLCK途径改善TJ完整性来实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d8/7963908/9a57a6972e3b/ECAM2021-6657141.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d8/7963908/e232570f55e4/ECAM2021-6657141.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d8/7963908/e232570f55e4/ECAM2021-6657141.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d8/7963908/c86b3848b032/ECAM2021-6657141.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d8/7963908/8c15244df103/ECAM2021-6657141.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d8/7963908/a40e206d0bf5/ECAM2021-6657141.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d8/7963908/cfb3a3e4c42b/ECAM2021-6657141.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d8/7963908/d61b519eefe7/ECAM2021-6657141.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d8/7963908/eb1ad19fc5e9/ECAM2021-6657141.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d8/7963908/72af05420cb5/ECAM2021-6657141.008.jpg
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