Licochalcone A in Inhibiting Bleomycin-induced Pulmonary Fibrosis Through TGF-β/Smad Pathway

Yu FU; Xia WU; Sui-qing CHEN

doi:10.13422/j.cnki.syfjx.20190402

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Licochalcone A in Inhibiting Bleomycin-induced Pulmonary Fibrosis Through TGF-β/Smad Pathway

Pharmacology | 更新时间：2021-02-09

- Licochalcone A in Inhibiting Bleomycin-induced Pulmonary Fibrosis Through TGF-β/Smad Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 4, Pages: 94-100(2019)
- 作者机构：
  
  1.河南中医药大学　药学院，呼吸病协同创新中心，郑州　 450046；
  2.河南省人民医院，郑州　 450000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190402
  CLC： R2-0;R22;R285.5
- Received：16 July 2018，
  
  Published Online：05 November 2018，
  
  Published：20 February 2019
- 稿件说明：
移动端阅览
Yu FU, Xia WU, Sui-qing CHEN. Licochalcone A in Inhibiting Bleomycin-induced Pulmonary Fibrosis Through TGF-β/Smad Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(4): 94-100.
DOI：

Yu FU, Xia WU, Sui-qing CHEN. Licochalcone A in Inhibiting Bleomycin-induced Pulmonary Fibrosis Through TGF-β/Smad Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(4): 94-100. DOI： 10.13422/j.cnki.syfjx.20190402.

摘要

目的：

探索甘草查而酮A对博来霉素(bleomycin，BLM)诱导小鼠肺纤维化的治疗作用，并探讨其相关的作用机制。

方法：

本研究将30只小鼠随机平均分为5组，分别为正常组、模型组、甘草查尔酮A高、低剂量组、吡非尼酮组。气管滴注BLM 5 mg·kg

－1

建立小鼠肺纤维化模型，次日治疗组灌胃给予甘草查尔酮A 15，30 mg·kg

－1

，吡非尼酮300 mg·kg

－1

，其余组给予生理盐水灌胃，28 d后处死小鼠。取肺组织称质量，进行肺组织苏木素-伊红(HE)染色和马松(Masson)染色、测定肺组织羟脯氨酸含量、通过蛋白免疫印迹法(Western blot)分析肺组织

-平滑肌肌动蛋白(

-SMA)，I型胶原蛋白(Collagen I)，纤连蛋白(FN)以及p-Smad2/3与Smad2/3表达水平。并考察甘草查尔酮A对转化生长因子-

(TGF-

)诱导成纤维细胞MRC-5细胞活化作用。

结果：

与正常组比较，模型组小鼠可见肺泡结构有不同程度的破坏，肺间质增生，有炎细胞浸润和胶原纤维增生形成，肺组织中羟脯胺酸，

-SMA，Collagen I蛋白表达水平明显增加(

0.05，

0.01)；与模型组比较，各治疗组小鼠的肺指数明显下降(

0.05，

0.01)，肺损伤与纤维化程度显著改善；肺组织的羟脯氨酸含量，

-SMA，Collagen I蛋白表达水平明显降低(

0.05，

0.01)；肺组织的Smad2/3蛋白磷酸化水平显著降低(

0.05，

0.01)；另外，甘草查尔酮A与吡非尼酮显著抑制TGF-

诱导MRC-5细胞转化，明显降低

-SMA，FN蛋白表达(

0.05，

0.01)。

结论：

甘草查而酮A可能通过阻断Smad相关信号通路，抑制成纤维细胞转化等发挥抗纤维化作用。

Abstract

Objective:

To explore the therapeutic effect of licochalcone A (Lico A) on pulmonary fibrosis (PF).

Method:

Thirty mice were divided into five group

namely sham

model

Lico A (15

30 mg·kg

-1

) and pirfenidone (300 mg·kg

-1

) groups. All of the groups except for sham group were intratracheally given bleomycin (BLM

5 mg·kg

-1

). The sham group was given normal saline. On day 2

the mice were treated with Lico A and pirfenidone

respectively. On day 28

all of the mice were put to death. Then

lung tissues were collected and weighted. Pathological changes in lung tissue were measured by htoxylin eosin(HE) and Masson staining. The

-smooth muscle actin(

-SMA)

Collagen I

fibronectin p-Smad2/3 and Smad2/3 were analyzed by Western blot. Then

transforming growth factor-

(TGF-

)-induced MRC-5 cells were employed for evaluating the inhibitory activity of Lico A

in vitro

Result:

Compared with normal group

several pathological changes

including alveolar space collapse

emphysema

infiltration of inflammatory cells

and collagen deposition were observed in the BLM-treated mice

and these pathological changes were markedly attenuated by subsequent treatment with Lico A. Lico A could significantly inhibit BLM-induced up-regulation of

-SMA and Collagen I and phosphorylation of Smad2/3 in lung tissues of mice(

0.05

0.01). In addition

Lico A could significantly suppressed TGF-

-induced

-SMA and fibronectin expression in MRC-5 cells(

0.05

0.01).

Conclusion:

The preliminary mechanisms of the anti-fibrosis effect of Lico A may inhibit TGF-

/Smad pathway.

关键词

Keywords

references

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