Shenling Baizhusan Alleviates Intestinal Inflammation in Rat Model of Crohn's Disease via p38 MAPK Pathway

YIN Yuanyuan; BIN Donghua; CHENG Yang; ZOU Weiying; LIU Ying; HUANG Jingwen; YU Lian

doi:10.13422/j.cnki.syfjx.20230716

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Shenling Baizhusan Alleviates Intestinal Inflammation in Rat Model of Crohn's Disease via p38 MAPK Pathway

更新时间：2023-09-08

- Shenling Baizhusan Alleviates Intestinal Inflammation in Rat Model of Crohn's Disease via p38 MAPK Pathway
  增强出版
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 19, Pages: 9-17(2023)
- 作者机构：
  
  1.湖南中医药大学，长沙 410208
  2.湖南中医药大学第一附属医院，长沙 410007
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230716
  CLC： R284;R285;R289;R287;R22;R2-031;R33;R24
- Published：05 October 2023，
  
  Published Online：25 June 2023，
  
  Received：21 March 2023，
- 稿件说明：
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尹园缘,宾东华,程扬等.基于p38 MAPK通路探究参苓白术散对克罗恩病大鼠肠道炎症反应的影响[J].中国实验方剂学杂志,2023,29(19):9-17.

YIN Yuanyuan,BIN Donghua,CHENG Yang,et al.Shenling Baizhusan Alleviates Intestinal Inflammation in Rat Model of Crohn's Disease via p38 MAPK Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(19):9-17.
尹园缘,宾东华,程扬等.基于p38 MAPK通路探究参苓白术散对克罗恩病大鼠肠道炎症反应的影响[J].中国实验方剂学杂志,2023,29(19):9-17. DOI： 10.13422/j.cnki.syfjx.20230716.

YIN Yuanyuan,BIN Donghua,CHENG Yang,et al.Shenling Baizhusan Alleviates Intestinal Inflammation in Rat Model of Crohn's Disease via p38 MAPK Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(19):9-17. DOI： 10.13422/j.cnki.syfjx.20230716.

摘要

目的

观察参苓白术散对克罗恩病（CD）大鼠肠道炎症反应的影响及其与p38丝裂原活化蛋白激酶（MAPK）信号通路的关系，通过对各组间作用差异的对比，为该方在临床广泛应用提供一定的实验及理论依据。

方法

SD大鼠共72只，随机被分作正常组（12只）、造模组（60只），雌雄各半。造模组大鼠应用2，4，6-三硝基苯磺酸（TNBS）（3 mL·kg

-1

）造模，随后被平均分作模型组、美沙拉嗪组（0.21 g·kg

-1

·d

-1

）、参苓白术散低、中、高剂量组（5.88、11.76、23.59 g·kg

-1

·d

-1

）。药物组大鼠应用相应药物进行灌胃14 d，正常组与模型组则应用等体积的蒸馏水灌胃。灌胃结束后进行各组大鼠炎症性肠病（IBD）炎症活动指数（DAI）评分及结肠黏膜损伤指数（CMDI）评分；苏木精-伊红（HE）染色观察各组大鼠结肠组织病理学改变；酶联免疫吸附测定法（ELISA）检测各组大鼠血清中肿瘤坏死因子-

（TNF-

）、白细胞介素-1（IL-1）、白细胞介素-6（IL-6）的含量；蛋白质免疫印迹法（Western blot）检测各组大鼠结肠组织中p38 MAPK、磷酸化-p38 MAPK（p-p38 MAPK）、65 kDa核转录因子-

B（NF-

B p65）、磷酸化-NF-

B p65（p-NF-

B p65）蛋白的表达水平；实时荧光定量聚合酶链式反应（Real-time PCR）检测大鼠结肠组织中p38 MAPK、NF-

B p65 miRNA的表达水平。

结果

与正常组比较，模型组大鼠在DAI评分、CMDI评分水平上有显著的升高（

0.01），病理学可见模型组结肠肠黏膜上皮细胞明显破损，腺体排列不规则，单管状的腺体被破坏，部可见坏死或消失，各层均可见大量炎症细胞与淋巴细胞浸润，有溃疡形成，模型组大鼠血清中TNF-

、IL-1、IL-6水平均显著升高（

0.01）；结肠组织中p-p38 MAPK、p-NF-

B p65的蛋白表达量及p38 MAPK miRNA的相对表达量有显著的升高（

0.01）；与模型组比较，美沙拉嗪组、参苓白术散高剂量组及中剂量组大鼠的DAI评分及CMDI评分均有明显改善（

0.05，

0.01），病理学表现中这3组大鼠结肠组织黏膜上皮基本修复，腺体、杯状细胞增加，血清中美沙拉秦组及参苓白术散高、中剂量组TNF-

、IL-1、IL-6水平明显下降（

0.05，

0.01），参苓白术散低剂量组TNF-

水平明显下降（

0.05），结肠黏膜p-p38 MAPK、p-NF-

B p65的蛋白表达量及p38 MAPK miRNA相对表达量明显降低（

0.05，

0.01）。

结论

参苓白术散对CD大鼠肠道炎症反应的减轻有一定的效果，其可能是通过下调p-p38 MAPK、p-NF-

B p65的蛋白表达及p38 MAPK miRNA的表达，抑制p38 MAPK通路从而缓解CD大鼠肠道炎症反应，促进结肠黏膜的修复。

Abstract

Objective

To observe the effect of Shenling Baizhusan on the intestinal inflammatory reaction in the rat model of Crohn's disease （CD） and study its relationship with p38 mitogen-activated protein kinase （MAPK） signaling pathway， so as to provide an experimental and theoretical basis for the clinical application of this prescription.

Method

A total of 72 SD rats （36 males and 36 females） were randomized into a normal group （

=12） and a modeling group （

=60）. The rats in the modeling group were treated with 2，4，6-trinitrobenzene sulfonic acid （TNBS， 3 mL·kg

-1

） and then randomized into model， mesalazine （0.21 g·kg

-1

·d

-1

）， and low-， medium-， and high-dose （5.88， 11.76， 23.59 g·kg

-1

·d

-1

， respectively） Shenling Baizhusan groups. The rats in the drug intervention groups were administrated with corresponding agents by gavage for 14 days， and those in the normal and model groups with an equal volume of distilled water. The disease activity index （DAI） score of inflammatory bowel disease （IBD） and the colon mucosal damage index （CMDI） score of rats in each group were assessed after gavage. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the colon， and enzyme-linked immunosorbent assay （ELISA） to measure the levels of tumor necrosis factor alpha （TNF-

）， interleukin-1 （IL-1）， and interleukin-6 （IL-6） in the serum. Western blotting was employed to determine the protein levels of p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， p65 nuclear factor （NF）-

B， and phosphorylated-p65 NF-

B （p-NF-

B p65） in the colon tissue. Quantitative real-time polymerase chain reaction was conducted to determine the miRNA levels of p38 MAPK and NF-

B p65 in the colon tissue.

Result

The model group had higher DAI and CMDI scores than the normal group （

0.01） and showed damaged epithelial cells in the colon mucosa， disarrangement of glands， damaged simple tubular glands， local necrosis， infiltration of a large number of inflammatory cells and lymphocytes in each layer， and presence of ulceration. Compared with the normal group， the model group showed elevated levels of TNF-

， IL-1， and IL-6 in the serum （

0.01） and up-regulated protein levels of p-p38 MAPK and p-NF-

B p65 and miRNA level of p38 MAPK in the colon tissue （

0.01）. Compared with the model group， mesalazine and high- and medium-dose Shenling Baizhusan decreased the DAI and CMDI scores （

0.05，

0.01）， repaired the mucosal epithelium of the colon tissue， increased the glands and goblet cells， lowered the levels of TNF-

， IL-1， and IL-6 in the serum （

0.05，

0.01）， and down-regulated the protein levels of p-p38 MAPK and p-NF-

B p65 and the miRNA level of p38 MAP in the colon mucosa （

0.01，

0.05）.

Conclusion

Shenling Baizhusan can reduce intestinal inflammation of CD rats and promote the repair of colon mucosa by down-regulating the protein levels of p-p38 MAPK and pNF-

B p65 and the miRNA level of p38 MAPK to inhibit the p38 MAPK pathway.

关键词

参苓白术散克罗恩病炎症反应p38分裂原活化蛋白激酶（MAPK）通路

Keywords

Shenling BaizhusanCrohn's diseaseinflammatory reactionp38 mitogen-activated protein kinase （MAPK） pathway

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