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J Zhejiang Univ (Med Sci)  2022, Vol. 51 Issue (1): 53-61    DOI: 10.3724/zdxbyxb-2021-0203
    
Efficacy of Qingfei oral liquid for idiopathic pulmonary fibrosis in rats and related network pharmacology study
ZHANG Yiwen,SHENG Kongsheng,SONG Feifeng,PAN Zongfu,ZOU Xiaozhou,LIU Yujia,HUANG Ping()
Department of Pharmacy, Clinical Pharmacy Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
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Abstract  

Objective:To investigate the therapeutic effect and mechanism of Qingfei oral liquid in idiopathic pulmonary fibrosis. Methods: Seventy-two male SD rats were divided into control group, model group, pirofenidone group and Qingfei group with 18 animals in each group. The idiopathic pulmonary fibrosis was induced in last three groups by intratracheal injection of 3?mg/kg bleomycin; pirofenidone group was given oral administration of 50?mg/kg pirofenidone b.i.d for 21?d, and Qingfei group was given Qingfei oral liquid 3.6?mL/kg q.d for 21?d. Lung tissues were obtained for HE staining, Masson staining and transforming growth factor (TGF)-β immunohistochemical staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were detected in tissue homogenates. The BATMAN-TCM database was used to retrieve the chemical components and their corresponding targets of Qingfei oral solution by network pharmacology method, and then the component-target-disease network diagram was constructed. Finally, the pathway enrichment analysis was carried out to explore the molecular mechanism of Qingfei oral liquid against idiopathic fibrosis. Results: Histopathology results showed that Qingfei oral liquid had a similar relieving effect on pulmonary fibrosis as the positive drug pirfenidone; TGF-β secretion had a significant reduction in lung tissues of Qingfei group; and Qingfei oral liquid had better regulatory effect on SOD, MDA and GSH than pirfenidone. The results of component-target-disease network and pathway enrichment analysis showed that the related molecular pathways were concentrated in inflammation, extracellular matrix and cytokines. Conclusion: Qingfei oral liquid has a good therapeutic effect on idiopathic pulmonary fibrosis in rats via regulation of inflammation, extracellular matrix and cytokines.



Key wordsIdiopathic pulmonary fibrosis      Qingfei oral liquid      Network pharmacology      Oxidation-reduction      Transforming growth factor-β      Rats     
Received: 18 July 2021      Published: 17 May 2022
CLC:  R965  
Corresponding Authors: HUANG Ping     E-mail: huangping@hmc.edu.cn
Cite this article:

ZHANG Yiwen,SHENG Kongsheng,SONG Feifeng,PAN Zongfu,ZOU Xiaozhou,LIU Yujia,HUANG Ping. Efficacy of Qingfei oral liquid for idiopathic pulmonary fibrosis in rats and related network pharmacology study. J Zhejiang Univ (Med Sci), 2022, 51(1): 53-61.

URL:

https://www.zjujournals.com/med/10.3724/zdxbyxb-2021-0203     OR     https://www.zjujournals.com/med/Y2022/V51/I1/53


清肺口服液在特发性肺纤维化中的治疗作用及网络药理学研究

目的:考察清肺口服液在特发性肺纤维化中的治疗作用及机制。方法:72只SD大鼠分为正常对照组、模型对照组、吡非尼酮组(给予吡非尼酮 50?mg·kg–1·次–1,每天2次)、清肺口服液组(给予清肺口服液3.6?mL/kg,每天1次)处理21?d,获取肺组织进行HE染色、马森染色和转化生长因子-β(TGF-β)免疫组织化学染色,其余组织进行匀浆后检测超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱苷肽(GSH)。采用网络药理学方法,利用BATMAN-TCM数据库检索清肺口服液组成药物的化学成分及其对应靶点,随后构建成分-靶点-疾病网络图,进行通路富集分析。结果:组织病理学结果提示,清肺口服液给药后可改善肺纤维化状态,且效果与吡非尼酮类似;清肺口服液可减少肺组织TGF-β表达,对SOD、MDA和GSH也有调控作用。成分-靶点-疾病网络构建及基因功能注释结果显示,清肺口服液与调控炎症、细胞外基质和细胞因子等通路相关。结论:清肺口服液可能通过调控炎症等信号通路发挥抗特发性肺纤维化作用。


关键词: 特发性肺纤维化,  清肺口服液,  网络药理学,  氧化还原,  转化生长因子-β,  大鼠 
Figure 1 Lung tissue morphology and fibrosis on day 21 (HE staining)
Figure 2 Collagen deposition changes in lung tissues on day 21 (masson staining)

 组别

第一周

第二周

第三周

±

+

++及以上

±

+

++及以上

±

+

++及以上

正常对照组

6

0

0

0

6

0

0

0

6

0

0

0

模型对照组

1

1

3

1

0

0

2

4

0

0

1

5

吡非尼酮组

3

1

2

0

0

0

5

1

2

0

3

1

清肺口服液组

1

3

1

1

1

0

0

5

0

0

6

0

P

>0.05

>0.05

<0.01

Table 1 Severity of lung fibrosis in each group
Figure 3 Transforming growth factor-β (TGF-β) expressions in lung tissues
Figure 4 GSH, SOD and MDA levels in lung tissues
Figure 5 The component-target-disease network diagram of Qingfei oral liquid in idiopathic pulmonary fibrosis treatment
Figure 6 The protein-protein interaction network of Qingfei oral liquid in idiopathic pulmonary fibrosis treatment
Figure 7 The top 10 up-regulated and down-regulated pathways related to Qingfei oral liquid in idiopathic pulmonary fibrosis treatment
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