糖肾方对糖尿病大鼠结肠Cajal间质细胞的保护作用

Peng-min CHEN; Jing-bo ZHAO; Xin YANG; Jing LI; Hao-jun ZHANG; Hui-cun ZHANG; Yu-ting ZHANG; Ping LI

doi:10.1007/s11655-021-3297-6

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糖肾方对糖尿病大鼠结肠Cajal间质细胞的保护作用

Original Article | Updated：2022-03-18

- 糖肾方对糖尿病大鼠结肠Cajal间质细胞的保护作用
- Protective Effect of Tangshen Formula on Interstitial Cells of Cajal in Colon of Diabetic Rats
- Chinese Journal of Integrative Medicine 2022年28卷第1期页码：43-51
- Affiliations：
  
  1.Beijing Key Lab Immune-Mediated Inflammatory Diseases,Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing (100029), China
  2.Department of Clinical Medicine, Aarhus University, Aarhus (8200), Denmark
  3.Department of Combination of Traditional Chinese and Western Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing (100010), China
- Author bio：
  
  Prof. LI Ping, E-mail: lp8675@163.com
- Funds：
  
  National Natural Science Foundation of China(81873135)
- DOI：10.1007/s11655-021-3297-6
  中图分类号：
- 纸质出版日期：2022-01-01，
  
  网络出版日期：2021-09-28，
  
  录用日期：2020-08-10
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Peng-min CHEN, Jing-bo ZHAO, Xin YANG, 等. 糖肾方对糖尿病大鼠结肠Cajal间质细胞的保护作用[J]. Chinese Journal of Integrative Medicine, 2022,28(1):43-51.

Peng-min CHEN, Jing-bo ZHAO, Xin YANG, et al. Protective Effect of Tangshen Formula on Interstitial Cells of Cajal in Colon of Diabetic Rats[J]. Chinese Journal of Integrative Medicine, 2022,28(1):43-51.
Peng-min CHEN, Jing-bo ZHAO, Xin YANG, 等. 糖肾方对糖尿病大鼠结肠Cajal间质细胞的保护作用[J]. Chinese Journal of Integrative Medicine, 2022,28(1):43-51. DOI： 10.1007/s11655-021-3297-6.

Peng-min CHEN, Jing-bo ZHAO, Xin YANG, et al. Protective Effect of Tangshen Formula on Interstitial Cells of Cajal in Colon of Diabetic Rats[J]. Chinese Journal of Integrative Medicine, 2022,28(1):43-51. DOI： 10.1007/s11655-021-3297-6.

摘要

目的:

探讨糖肾方对糖尿病大鼠结肠Cajal间质细胞的作用及其可能作用机制.

方法:

将8周龄雄性Wistar大鼠随机分为正常对照组 (

=14) 和高脂饮食组(

=40)

两组分别予普通饲料及高脂饲料喂养6周后

高脂组大鼠给予链脲佐菌素 (30 mg/kg

溶于柠檬酸缓冲液) 、正常对照组给予等剂量柠檬酸缓冲液腹腔注射一次. 3天后

将高脂组空腹血糖高于11.7 mmol/L的大鼠随机分为糖尿病组和糖肾方组

每组15只. 正常对照组及糖尿病组大鼠予生理盐水灌胃

糖肾方组给予糖肾方(2.4 g/kg)灌胃

每日1次

连续20周. 采用Western blot及免疫组化法检测结肠平滑肌Bax、Bcl-2和caspase-3表达水平; 采用特异性免疫组化染色

在光镜下对Cajal间质细胞计数; 采用特异性免疫荧光染色

分析经典激活型巨噬细胞 (M1) 和替代激活型巨噬细胞 (M2) 与总巨噬细胞的比例; 采用透射电镜观察上皮细胞超微结构和上皮间连接.

结果:

糖肾方可以增加高脂联合小剂量链脲佐菌素诱导的糖尿病大鼠结肠Cajal间质细胞数量(

0.05). 与正常组比较

糖尿病大鼠结肠Bcl-2、Bax、caspase-3及TNF-α表达水平升高、M1亚型巨噬细胞与总巨噬细胞比值增加(

0.05)

M2亚型巨噬细胞与总巨噬细胞比值降低(

0.05或

0.01); 与糖尿病组比较

糖肾方降低Bcl-2、Bax、caspase-3及TNF-α蛋白表达水平

部分逆转M2亚型巨噬细胞与总巨噬细胞的异常比值(

0.05 或

0.01)

并可改善糖尿病大鼠结肠上皮细胞的超微结构及上皮间的紧密和桥粒连接.

结论:

糖尿病大鼠结肠Cajal间质细胞数量减少可能与肠屏障的损伤有关. 糖肾方对Cajal间质细胞的保护作用可能是通过改善上皮连接

从而减轻糖尿病大鼠结肠的炎症和炎症引发的细胞凋亡.

Abstract

Objective:

To explore the effect of Tangshen Formula (TSF)

a Chinese herbal medicine

on interstitial cells of Cajal (ICC) in the colon of diabetic rats.

Methods:

Fifty-four male Wistar rats were randomly divided into normal control (NC

=14) and high-fat diet (HFD) groups (

=40). After 6 weeks

the rats in the HFD group were injected intraperitoneally streptozotocin once (30 mg/kg). Thirty rats with fasting blood glucose higher than 11.7 mmol/L were randomly divided into diabetes (DM) and TSF groups

15 rats in each group. Rats in the NC and DM groups were intragastrically administered with saline

and those in the TSF group were given with TSF (2.4 g/kg) once daily for 20 weeks. Expression levels of Bax

Bcl-2

and caspase-3 in colonic smooth muscle layer were measured by Western blotting and immunohistochemical staining. The number of ICC was determined by immunohistochemical staining. Immunofluorescence was used for analyzing the ratio of classically activated macrophages (M1) and alternatively activated macrophages (M2) to total macrophages. Electron microscopy was used to observe the epithelial ultrastructure and junctions.

Results:

TSF appeared to partially prevented loss of ICC in DM rats (

0.05). Compared with the NC group

expression levels of Bcl-2

Bax

caspase-3

and TNF-α as well as the ratio of M1 to total macrophages increased in DM rats (all

0.05)

and the ratio of M2 to total macrophages decreased (

0.05 or

0.01). Compared with the DM group

TSF decreased the expression levels of abovementioned proteins and restore M2 to total macrophages ratio (

0.05 or

0.01). TSF appeared to attenuate the ultrastructural changes of epithelia and improve the tight and desmosome junctions between epithelia reduced in the DM rats.

Conclusions:

Reduced number of ICC in DM rats may be associated with damage of the intestinal barrier. The protective effects of TSF on ICC may be through repair of the epithelial junctions

which attenuates inflammation and inflammation-initiated apoptosis in colon of DM rats.

关键词

Keywords

diabetesinterstitial cells of Cajaltight junctionintestinal epitheliamacrophageTangshen Formula

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