Impact of Wenyang Huazhuo Tongluo Formula on TGF-β1/Smad Signal Pathway of Systemic Sclerosis Mouse Model

BIAN Hua; LV Qin; HAN Li; YANG Lei; HU Jiulue; ZHANG Lifang

doi:10.13288/j.11-2166/r.2015.04.016

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Impact of Wenyang Huazhuo Tongluo Formula on TGF-β1/Smad Signal Pathway of Systemic Sclerosis Mouse Model

更新时间：2021-11-17

- Impact of Wenyang Huazhuo Tongluo Formula on TGF-β1/Smad Signal Pathway of Systemic Sclerosis Mouse Model
- Journal of Traditional Chinese Medicine Vol. 56, Issue 4, Pages: 327-331(2015)
- 作者机构：
  
  1. 南阳理工学院张仲景国医学院
  2. 南阳医学高等专科学校
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2015.04.016
  CLC： R285.5
- Published：2015
- 稿件说明：
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[1]卞华,吕芹,韩立,杨雷,胡久略,张瓅方.温阳化浊通络方对系统性硬化症模型小鼠TGF-β1/Smad信号通路的影响[J].中医杂志,2015,56(04):327-331.

BIAN Hua, LV Qin, HAN Li, et al. Impact of Wenyang Huazhuo Tongluo Formula on TGF-β1/Smad Signal Pathway of Systemic Sclerosis Mouse Model[J]. Journal of Traditional Chinese Medicine2015, 56(4): 327-331.
[1]卞华,吕芹,韩立,杨雷,胡久略,张瓅方.温阳化浊通络方对系统性硬化症模型小鼠TGF-β1/Smad信号通路的影响[J].中医杂志,2015,56(04):327-331. DOI： 10.13288/j.11-2166/r.2015.04.016.

BIAN Hua, LV Qin, HAN Li, et al. Impact of Wenyang Huazhuo Tongluo Formula on TGF-β1/Smad Signal Pathway of Systemic Sclerosis Mouse Model[J]. Journal of Traditional Chinese Medicine2015, 56(4): 327-331. DOI： 10.13288/j.11-2166/r.2015.04.016.

摘要

目的探讨温阳化浊通络方治疗系统性硬化症（SSc）的可能作用机制。方法将60只C3H/He小鼠随机分为正常组、模型组、西药组和中药低、中、高剂量组

每组10只。除正常组外其余各组给予皮下注射博莱霉素3周建立SSc小鼠模型。西药组小鼠灌服青霉胺片65 mg/（kg·d）

中药低、中、高剂量组分别灌服温阳化浊通络方水煎剂11.75、23.50、47.00 g/（kg·d）

模型组和正常组给予等体积的生理盐水

共干预8周。采用HE染色观察皮肤组织病理变化

采用RT-PCR法检测皮肤转化生长因子β1（TGF-β1）、Smad2、Smad7 mRNA表达

采用Western blot法检测皮肤Ⅰ、Ⅲ型胶原蛋白（COL-Ⅰ、COL-Ⅲ）表达。结果模型组较正常组皮肤真皮变厚

胶原增加、变粗

真皮小血管周围炎症细胞浸润

西药组和中药低、中、高各剂量组与模型组比较真皮变薄、胶原含量减少

血管周围炎症细胞浸润减轻。与正常组比较

模型组TGF-β1、Smad2 mRNA及COL-Ⅰ、COL-Ⅲ蛋白表达升高

Smad7 mRNA表达降低（P<0.01）;与模型组比较

西药组和中药低、中、高剂量组TGF-β1、Smad2 mRNA及COL-Ⅰ、COL-Ⅲ蛋白表达减少

Smad7 mRNA表达增加（P<0.05或P<0.01）;中药高剂量组TGF-β1、Smad2、Smad7 mRNA及COL-Ⅰ、COL-Ⅲ蛋白表达改善优于西药组和中药低剂量组（P<0.05或P<0.01）。结论温阳化浊通络方可拮抗SSc纤维化

可能与干预TGF-β1/Smad信号通路、降低皮肤胶原蛋白含量有关

且高剂量效果更佳。

Abstract

Objective To discuss the possible mechanism of Wenyang Huazhuo Tongluo Formula（ WYHZTLF）in the treatment of systemic sclerosis（ SSc）. Methods In total 60 C3 H / He mice were randomly divided into normal group

model group

western medicine group and the low

medium and high dose TCM groups

with 10 in each.Except for the normal group

all groups were injected with bleomycin subcutaneously for 3 weeks to make the SSc mouse model. The western medicine group was given penicillamine tablets 65 mg /（ kg·d） by gavage

while the low

medium and high dose TCM groups were given 11. 75 g /（ kg·d）

23. 5 g /（ kg·d）

or 47 g /（ kg·d） of WYHZTLF decoction respectively

and the model group and normal group were given the equal volume of saline. Treatments for all groups lasted for 8 weeks. Pathological changes of skin tissues were observed using HE staining. The expression of skin transforming growth factor-β1（ TGF-β1）

Smad 2 and Smad 7 mRNA

type Ⅰ and Ⅲ collagen（ COL-Ⅰ

COL-Ⅲ） in the skin was tested. Results The dermis of the model group was thicker than the normal group

with more and thicker collagen

as well as infiltration of inflammatory cells around small vessels

while the western medicine group and all TCM groups showed thinner dermis compared with the model group

with less collagen content and infiltration of inflammatory cells. Compared with the normal group

the expression of TGF-β1

Smad 2 mRNA

COL-Ⅰand COL-Ⅲ protein in the model group increased

while the expression of Smad 7 mRNA decreased（ P < 0. 01）.Compared with the model group

the expression of TGF-β1

Smad 2 mRNA

COL-Ⅰ and COL-Ⅲ in the western medicine group and all TCM groups decreased

while the expression of Smad 7 mRNA increased（ P < 0. 05 or P <0. 01）. Improvements on the expression of TGF-β1

Smad 2

Smad 7 mRNA

COL-Ⅰ and COL-Ⅲ in high dose TCM group was better than that in the western medicine group and low dose TCM group（ P < 0. 05 or P < 0. 01）.Conclusion WYHZTLF could antagonize the fibrosis in SSc

which could be related to its regulation of TGF-β1 /Smad signal pathway and reduction of collagen content. This effect of WYHZTLF is better when dose is high.

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Related Institution

School of Acupuncture，Moxibustion and Tuina， Fujian University of Traditional Chinese Medicine

Clinical Medical College， Jiangxi University of Traditional Chinese Medicine

The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine

School of Traditional Chinese Medicine， Jiangxi University of Traditional Chinese Medicine

Xiyuan Hospital,China Academy of Chinese Medical Sciences

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