基于HMGB1/TLR4/NF-<italic style="font-style: italic">κ</italic>B通路探讨桃仁承气汤调节肠源性脓毒症大鼠肠道肌电活动及微环境稳态的作用机制

王丽辉; 孙治霞; 索红亮; 郭艳青; 袁彬; 李宗尚; 李莉

doi:10.13422/j.cnki.syfjx.20201239

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基于HMGB1/TLR4/NF-κB通路探讨桃仁承气汤调节肠源性脓毒症大鼠肠道肌电活动及微环境稳态的作用机制

经典名方 | 更新时间：2020-08-11

- 基于HMGB1/TLR4/NF-κB通路探讨桃仁承气汤调节肠源性脓毒症大鼠肠道肌电活动及微环境稳态的作用机制
- Study on Mechanism of Taoren Chengqitang in Regulating Intestinal Myoelectrical Activity and Microenvironment Homeostasis in Intestinal Sepsis Rats Based on HMGB1/TLR4/NF-κB Pathway
- 中国实验方剂学杂志 2020年26卷第12期页码：78-84
- 作者机构：
  
  河南中医药大学第二附属医院，郑州 450002
- 作者简介：
  
  王丽辉，副主任医师，从事脓毒症基础与临床研究，E-mail：lihuiwang972@163.com
- 基金信息：
  
  河南省中医药科学研究专项(2018ZY2050)
- DOI：10.13422/j.cnki.syfjx.20201239
  中图分类号： R2-0;R289;R373.1;R574.4
- 网络出版日期：2020-04-08，
  
  纸质出版日期：2020-06-20
- 稿件说明：
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王丽辉,孙治霞,索红亮等.基于HMGB1/TLR4/NF-κB通路探讨桃仁承气汤调节肠源性脓毒症大鼠肠道肌电活动及微环境稳态的作用机制[J].中国实验方剂学杂志,2020,26(12):78-84.

WANG Li-hui,SUN Zhi-xia,SUO Hong-liang,et al.Study on Mechanism of Taoren Chengqitang in Regulating Intestinal Myoelectrical Activity and Microenvironment Homeostasis in Intestinal Sepsis Rats Based on HMGB1/TLR4/NF-κB Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(12):78-84.
王丽辉,孙治霞,索红亮等.基于HMGB1/TLR4/NF-κB通路探讨桃仁承气汤调节肠源性脓毒症大鼠肠道肌电活动及微环境稳态的作用机制[J].中国实验方剂学杂志,2020,26(12):78-84. DOI： 10.13422/j.cnki.syfjx.20201239.

WANG Li-hui,SUN Zhi-xia,SUO Hong-liang,et al.Study on Mechanism of Taoren Chengqitang in Regulating Intestinal Myoelectrical Activity and Microenvironment Homeostasis in Intestinal Sepsis Rats Based on HMGB1/TLR4/NF-κB Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(12):78-84. DOI： 10.13422/j.cnki.syfjx.20201239.

摘要

目的

基于高迁移率族蛋白B1（HMGB1）/Toll样受体4（TLR4）/核转录因子-

B（NF-

B）通路研究桃仁承气汤调节肠源性脓毒症大鼠肠道肌电活动及微环境稳态的作用机制。

方法

60只SD大鼠随机分为假手术组、模型组、甘草酸（HMGB1抑制剂，0.03 g·kg

-1

）组、桃仁承气汤（10 g·kg

-1

）组、甘草酸+桃仁承气汤（0.03 g·kg

-1

+10 g·kg

-1

）组，每组12只。除假手术组外，其余各组建立肠源性脓毒症大鼠模型，各组分别以药物处理后，采用苏木素-伊红（HE）染色检测各组大鼠小肠黏膜组织病理改变，比较黏膜厚度、绒毛高度变化；采用试剂盒检测各组大鼠小肠黏膜组织分泌型免疫球蛋白A（sIgA）含量，血清二胺氧化酶（DAO）及

-乳酸水平；检测各组大鼠肠道肌电活动，比较小肠平滑肌慢波频率、慢波振幅；检测各组大鼠肠道菌群，比较大肠埃希菌、双歧杆菌和乳酸杆菌含量；采用蛋白免疫印迹法（Western blot）检测小肠组织中HMGB1/TLR4/NF-

B通路蛋白HMGB1，TLR4，MyD88，NF-

B p65表达情况。

结果

与假手术组比较，模型组大鼠小肠黏膜组织绒毛高度、黏膜厚度，sIgA含量，平滑肌慢波频率及振幅、肠道双歧杆菌及乳酸杆菌含量显著降低，血清DAO及

D-

乳酸水平、肠道大肠埃希菌含量、小肠组织HMGB1，TLR4，MyD88及NF-

B p65蛋白表达明显升高（

0.05）；与模型组比较，桃仁承气汤组、甘草酸组、甘草酸+桃仁承气汤组大鼠小肠黏膜组织绒毛高度、黏膜厚度，sIgA含量、平滑肌慢波频率及振幅、肠道双歧杆菌及乳酸杆菌含量升高，血清DAO及

D-

乳酸水平、肠道大肠埃希菌含量、小肠组织HMGB1，TLR4，MyD88及NF-

B p65蛋白表达降低（

0.05）；与桃仁承气汤组、甘草酸组分别比较，甘草酸+桃仁承气汤组大鼠小肠黏膜组织绒毛高度、黏膜厚度，sIgA含量、平滑肌慢波频率及振幅、肠道双歧杆菌及乳酸杆菌含量升高，血清DAO及

-乳酸水平、肠道大肠埃希菌含量、小肠组织HMGB1，TLR4，MyD88及NF-

B p65蛋白表达降低，差异均有统计学意义（

0.05）。

结论

桃仁承气汤可减轻小肠黏膜损伤，调控肠源性脓毒症大鼠肠道肌电活动及微环境稳态，恢复肠道功能，保持菌群平衡，可能是通过下调HMGB1/TLR4/NF-

B通路实现的。

Abstract

Objective

To study the mechanism of Taoren Chengqitang in regulating intestinal myoelectric activity and microenvironment homeostasis in intestinal sepsis rats based on high mobility group protein 1(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor -

B(NF-

B) pathway.

Method

The 60 SD rats were randomly divided into sham operation group

model group

glycyrrhizic acid (HMGB1 inhibitor

0.03 g·kg

-1

) group

Taoren Chengqitang group (10 g·kg

-1

)

glycyrrhizic acid+Taoren Chengqitang group (0.03 g·kg

-1

+10 g·kg

-1

)

with 12 rats in each group. Except the sham operation group

the other groups established intestinal sepsis rat models

each group was treated with medicine

hematoxylin-eosin (HE) staining was used to detect the histopathological changes of small intestinal mucosa in rats of each group

the changes of mucosal thickness and villus height were compared

the levels of secretory immunoglobulin A (sIgA)

diamine oxidase (DAO) and

D-

lactic acid in intestinal mucosa of rats were detected by kit

the intestinal myoelectrical activity of rats in each group was measured

the slow wave frequency and amplitude of small intestinal smooth muscle were compared

the intestinal flora of rats in each group was detected

the contents of

E. coli

Bifidobacterium

and

Lactobacillus

were compared

and the expressions of HMGB1/TLR4/NF-

B pathway proteins HMGB1

TLR4

MyD88 and NF-

B p65 in small intestinal tissues were detected by Western blot.

Result

Compared with sham operated group

the villus height

mucosal thickness

sIgA content

slow wave frequency and amplitude of smooth muscle

Bifidobacterium

and

Lactobacillus

contents in intestinal mucosa of model group rats were significantly decreased

and serum DAO and

D-

lactic acid levels

intestinal

E. coli

content

intestinal tissue HMGB1

TLR4

MyD88 and NF-

B p65 proteins were significantly increased (

0.05). Compared with the model group

the villus height

mucosal thickness

sIgA content

slow wave frequency and amplitude of smooth muscle

Bifidobacterium

and

Lactobacillus

contents in intestinal mucosa of the Taoren Chengqitang group

glycyrrhizic acid group

and glycyrrhizic acid + Taoren Chengqitang group were significantly increased

and serum DAO and

D-

lactic acid levels

intestinal

E. coli

content

intestinal tissue HMGB1

TLR4

MyD88 and NF-

B p65 proteins were significantly decreased (

0.05). Compared with the Taoren Chengqitang group and the glycyrrhizic acid group

the villus height

mucosal thickness

sIgA content

slow wave frequency and amplitude of smooth muscle

Bifidobacterium

and

Lactobacillus

contents in intestinal mucosa of glycyrrhizic acid+Taoren Chengqitang group were significantly increased

and serum DAO and

D-

lactic acid levels

intestinal

E. coli

content

intestinal tissue HMGB1

TLR4

MyD88 and NF-

B p65 proteins were significantly decreased

the differences were statistically significant (

0.05).

Conclusions

Taoren Chengqitang can alleviate intestinal mucosal injury

regulate intestinal myoelectrical activity and microenvironment homeostasis

restore intestinal function and maintain flora balance in intestinal sepsis rats

which may be achieved by down-regulating HMGB1/TLR4/NF-

B pathway.

关键词

Keywords

references

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桃仁承气汤对脓毒症大鼠肠黏膜屏障及TLR9信号通路的影响

基于HMGB1/TLR4/NF-κB通路探讨桃仁承气汤调节肠源性脓毒症大鼠肠道肌电活动及微环境稳态的作用机制

Study on Mechanism of Taoren Chengqitang in Regulating Intestinal Myoelectrical Activity and Microenvironment Homeostasis in Intestinal Sepsis Rats Based on HMGB1/TLR4/NF-κB Pathway

DOI：10.13422/j.cnki.syfjx.20201239

摘要

Abstract

关键词

Keywords

references