Effect of Xielitang on TLR4/NF-<italic style="font-style: italic">κ</italic>B/HIF-1<italic style="font-style: italic">α</italic> Signaling Pathway in Mice with Ulcerative Colitis

WANG Xiaotian; WANG Yue; BIAO Yaning; GAO Jingmiao; LI Li; LU-AI Yangzi; YIN Yunjie; ZHANG Yixin

doi:10.13422/j.cnki.syfjx.20230239

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Effect of Xielitang on TLR4/NF-κB/HIF-1α Signaling Pathway in Mice with Ulcerative Colitis

更新时间：2023-05-17

- Effect of Xielitang on TLR4/NF-κB/HIF-1α Signaling Pathway in Mice with Ulcerative Colitis
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 8, Pages: 142-149(2023)
- 作者机构：
  
  1.河北中医学院，河北省中药资源利用与质量评价国际联合研究中心，河北省高校中药组方制剂应用技术研发中心，石家庄 050200
  2.河北省沧州中西医结合医院中药药学部，河北沧州 061001
  3.河北医科大学药学院，石家庄 050011
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230239
  CLC： R2-0;R33;R289;R22;R318.14
- Published：20 April 2023，
  
  Published Online：02 February 2023，
  
  Received：28 November 2022，
- 稿件说明：
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王小天,王月,彪雅宁等.燮理汤对溃疡性结肠炎小鼠TLR4/NF-κB/HIF-1α通路的影响[J].中国实验方剂学杂志,2023,29(08):142-149.

WANG Xiaotian,WANG Yue,BIAO Yaning,et al.Effect of Xielitang on TLR4/NF-κB/HIF-1α Signaling Pathway in Mice with Ulcerative Colitis[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(08):142-149.
王小天,王月,彪雅宁等.燮理汤对溃疡性结肠炎小鼠TLR4/NF-κB/HIF-1α通路的影响[J].中国实验方剂学杂志,2023,29(08):142-149. DOI： 10.13422/j.cnki.syfjx.20230239.

WANG Xiaotian,WANG Yue,BIAO Yaning,et al.Effect of Xielitang on TLR4/NF-κB/HIF-1α Signaling Pathway in Mice with Ulcerative Colitis[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(08):142-149. DOI： 10.13422/j.cnki.syfjx.20230239.

摘要

目的

探讨燮理汤对葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎（UC）小鼠的保护作用及其可能的作用机制。

方法

60只C57BL/6小鼠随机分为正常组、模型组、柳氮磺吡啶组（0.6 g·kg

-1

）和燮理汤低、中、高剂量组（1.67、3.34、6.68 g·kg

-1

），以DSS溶液自由饮用周期循环的方式复制慢性UC小鼠模型。除正常组外，其余各组小鼠采用浓度为1.5%的DSS循环饮用3个周期（1~7 d，22~28 d，43~49 d），其余时间予以蒸馏水（8~21 d，29~42 d，50~63 d），待第1次循环结束后，给予相应的药物治疗42 d。实验过程中每日记录小鼠一般状况、体质量及疾病活动指数（DAI）评分的改变。治疗结束后，采集血清和结肠组织标本，测量结肠长度，计算肠重指数和结肠黏膜损伤（CMDI）评分；苏木素-伊红（HE）染色观察结肠组织病理形态学；酶联免疫吸附测定法（ELISA）检测血清中白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、肿瘤坏死因子-

（TNF-

）的含量；实时荧光定量聚合酶链式反应（Real-time PCR）和蛋白免疫印迹法（Western blot）检测结肠组织中Toll样受体4（TLR4）、核转录因子-

B（NF-

B）、缺氧诱导因子-1

（HIF-1

）mRNA和蛋白表达水平。

结果

与正常组比较，模型组小鼠体质量、结肠长度和IL-10含量均显著降低（

0.01），DAI评分、肠重指数、CMDI评分、IL-6、TNF-

含量及TLR4、NF-

B、HIF-1

mRNA和蛋白表达水平均显著升高（

0.01）；结肠黏膜结构破坏，出现炎性细胞浸润。与模型组比较，燮理汤各剂量组小鼠体质量、结肠长度和IL-10含量均明显升高（

0.05，

0.01），DAI评分、肠重指数和CMDI评分、IL-6、TNF-

含量及TLR4、NF-

B、HIF-1

mRNA和蛋白表达水平均明显降低（

0.05，

0.01）；结肠黏膜病理损伤明显减轻。

结论

燮理汤能明显改善DSS诱导的UC小鼠的炎症反应，其作用机制可能与调节TLR4/NF-

B/HIF-1

信号通路有关。

Abstract

Objective

To explore the protective effect of Xielitang on ulcerative colitis （UC） mice induced by dextran sodium sulfate （DSS） and its possible mechanism.

Method

Sixty C57BL/6 mice were randomly divided into normal group， model group， sulfasalazine group and and low-， medium-， and high-dose Xielitang groups. Free drinking DSS solution to build the chronic UC model mice. Except for normal group， other groups were given 1.5% DSS for 3 cycles of drinking （days 1-7， days 22-28 and days 43-49） and distilled water for the rest of the time （days 8-21， days 29-42 and days 50-63）. After the first cycle， corresponding drugs were given for 42 days. The changes of general condition， body weight and disease activity index （DAI） score of mice were daily recorded during the experiment. At the end of the treatment， serum and colon tissue samples were collected， colon length was measured， intestinal weight index and colonic mucosal injury （CMDI） score were calculated. The pathological status of colon tissue was observed by hematoxylin-eosin （HE） staining. The levels of interleukin-6 （IL-6）， interleukin-10 （IL-10） and tumour necrosis factor-

（TNF-

） were measured by enzyme-linked immunosorbent assay （ELISA）. The gene and protein expressions of Toll like receptor 4 （TLR4）， nuclear transcription factor-

B （NF-

B） and hypoxia inducible factor-1

（HIF-1

） in colon tissue was detected by Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot.

Result

Compared with the normal group， the body weight， colon length and IL-10 content in the model group were significantly decreased （

0.01）， DAI score， intestinal weight index， CMDI score， IL-6 and TNF-

contents， and mRNA and protein expression levels of TLR4， NF-

B and HIF-1

in the model group were significantly increased （

0.01）. Moreover， the structure of colonic mucosa was destroyed and inflammatory cells infiltrated in the model group. Compared with model group， body weight， colon length and IL-10 content in each dose group of Xielitang were significantly increased （

0.05，

0.01）， DAI score， intestinal weight index and CMDI score， IL-6 and TNF-

contents， mRNA and protein expression levels of TLR4， NF-

B and HIF-1

were notably decreased （

0.05，

0.01）. The pathological injury of colon was obviously alleviated.

Conclusion

Xielitang can significantly improve the inflammatory response of UC mice induced by DSS， and its mechanism may be related to the regulation of TLR4/NF-

B/HIF-1

signaling pathway.

关键词

燮理汤溃疡性结肠炎葡聚糖硫酸钠Toll样受体4核转录因子-κB缺氧诱导因子-1α

Keywords

Xielitangulcerative colitisdextran sodium sulfateToll like receptor 4 （TLR4）nuclear transcription factor-κB （NF-κB）hypoxia inducible factor-1α （HIF-1α）

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⁰

Effect of Xielitang on TLR4/NF-κB/HIF-1α Signaling Pathway in Mice with Ulcerative Colitis

DOI：10.13422/j.cnki.syfjx.20230239

摘要

Abstract

关键词

Keywords

references