The Effects of Wenfei Huaxian Decoction （温肺化纤汤） on Pulmonary Fibrosis and Endoplasmic Reticulum Stress in Systemic Sclerosis-Associated Interstitial Lung Disease Model Mice
10.13288/j.11-2166/r.2024.13.013
- VernacularTitle:温肺化纤汤对系统性硬化症相关间质性肺病模型小鼠肺组织纤维化及内质网应激的影响
- Author:
Mingliang QIU
1
;
Jiali XIONG
2
;
Chenxiao XIAO
1
;
Xinzhu ZHOU
1
;
Lisha MO
1
;
Shiwen KE
1
;
Guoshuang ZHU
2
;
Liangji LIU
1
Author Information
1. Clinical Medical College， Jiangxi University of Traditional Chinese Medicine， Nanchang， 330004
2. School of Traditional Chinese Medicine， Jiangxi University of Traditional Chinese Medicine
- Publication Type:Journal Article
- Keywords:
systemic sclerosis;
interstitial lung disease;
Wenfei Huaxian Decoction （温肺化纤汤）;
endoplasmic reti-culum stress;
nuclear factor kappa B
- From:
Journal of Traditional Chinese Medicine
2024;65(13):1383-1391
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the possible mechanism of Wenfei Huaxian Decoction （温肺化纤汤） in treatment of pulmonary fibrosis in systemic sclerosis-associated interstitial lung disease （SSc-ILD）. MethodsSixty C3H/He female rats were randomly divided into a control group， a model group， a pirfenidone group， and low-， medium-， and high-dose Wenfei Huaxian Decoction groups. The SSc-ILD model mice was established by subcutaneous injection of bleomycin solution 0.04 mg/d into the back of mice for 28 days in all groups but the control group. After successful modelling， the pirfenidone group was given pirfenidone capsule 300 mg/（kg·d） by gavage， the low-， medium- and high-dose Wenfei Huaxian Decoction groups were given Wenfei Huaxian Decoction 7.81， 15.62， and 31.24 g/（kg·d） by gavage， respectively， and the control group as well as the model group were given normal saline 0.1 ml/10 g by gavage， for a total of 21 days. At the end of the intervention， HE staining and Masson staining were used to observe the pathological changes in the skin and lung tissues； the hydroxyproline content of the skin and lung tissues was detected； the protein expression levels of endoplasmic reticulum stress-related proteins glucose-regulated protein 78 （BIP） and C/EBP homologous protein （CHOP） as well as those of nuclear factor kappa B （NF-κB） pathway p65 were measured by western blot； ELISA was performed to determine the expression levels of interferon gamma （IFN-γ）， interleukin 6 （IL-6） and tumour necrosis factor alpha （TNF-α） in serum of rats. ResultsThe results of HE and Masson staining indicated that compared with the control group， the dermis significantly thickened， the number of collagen fibers significantly enlarged， and the number of inflammatory cells significantly increased in the model group； the lung tissue showed a marked inflammatory cellular response with massive collagen fibre proliferation with inflammatory cell infiltration. Compared with the model group， the skin tissue and lung tissue collagen fibre proliferation significantly reduced and inflammatory cell infiltration reduced in the pirfenidone group and all dose groups of Wenfei Huaxian Decoction， and the effects of pirfenidone group and Wenfei Huaxian Decoction medium- and high-dose groups were basically comparable. Compared with the model group， the content of hydroxyproline in skin and lung tissue， the serum level of IFN-γ， IL-6 and TNF-α， and the expression levels of BIP and CHOP protein in lung tissue increased in model group （P＜0.05）. Compared with model group， the content of hydroxyproline in skin tissue of pirfenidone group， low-and medium-dose Wenfei Huaxian Decoction groups decreased， and the content of hydroxyproline in lung tissue of medium-dose Wenfei Huaxian Decoction group decreased. The serum level of IFN-γ， IL-6， TNF-α and the expression levels of BIP， CHOP and p65 protein in lung tissue of rats in pirfenidone group and high-dose Wenfei Huaxian Decoction group decreased （P＜0.05）. The content of hydroxyproline in lung tissue of medium-dose Wenfei Huaxian Decoction group was significantly lower than that of low-dose and high-dose Wenfei Huaxian Decoction group， and the serum level of IFN-γ， IL-6， TNF-α in low- and medium-dose Wenfei Huaxian Decoction group were higher than those in high-dose Wenfei Huaxian Decoction group. The expression level of BIP protein in high-dose group was significantly lower than that in low- and medium-dose Wenfei Huaxian Decoction groups （P＜0.05）. ConclusionWenfei Huaxian Decoction can improve the skin and lung fibrosis of SSc-ILD rats， which may act through anti-inflammation， inhibition of NF-κB pathway， and then inhibition of endoplasmic reticulum stress， which ultimately blocked the fibrotic process.
