Dexamethasone combined with berberine is an effective therapy for bleomycin‑induced pulmonary fibrosis in rats

Li,Li; Li,Qiuhong; Wei,Lei; Wang,Zhongfu; Ma,Wei; Liu,Fangying; Shen,Yanhua; Zhang,Shanfang; Zhang,Xiulian; Li,Huiping; Qian,Yechang

doi:10.3892/etm.2019.7861

Dexamethasone combined with berberine is an effective therapy for bleomycin‑induced pulmonary fibrosis in rats

Authors:
- Li Li
- Qiuhong Li
- Lei Wei
- Zhongfu Wang
- Wei Ma
- Fangying Liu
- Yanhua Shen
- Shanfang Zhang
- Xiulian Zhang
- Huiping Li
- Yechang Qian
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Affiliations: Department of Respiratory Disease, Baoshan Branch, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200431, P.R. China, Department of Respiratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, P.R. China
Published online on: August 7, 2019 https://doi.org/10.3892/etm.2019.7861
Pages: 2385-2392
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pulmonary fibrosis (PF) is a heterogeneous pathological process in lung tissues with a considerable mortality rate. Currently, combination therapy represents an effective approach to treat PF. Dexamethasone (Dxs) and berberine (BBR) are widely applied to inhibit the progression of PF. Dxs plus penehyclidine hydrochloride or alfacalcidol have been reported more effective in therapy compared with any single drug treatment. However, whether Dxs plus BBR induces an increased antifibrotic effect remains unknown. The current study aimed to evaluate the therapeutic effect of BBR plus Dxs in bleomycin (BLM)‑induced PF. A PF model in rats was established and rats were divided into control, BLM, BBR, Dxs and BBR plus Dxs groups (n=9/group). On days 3, 7 and 14, blood samples were collected from the eyes of the rats (n=6/group). CXC chemokine ligand 14 (CXCL14), collagen I, collagen III, matrix metalloproteinase (MMP)2 and MMP9 serum levels were measured by ELISA. On day 14, all rats were sacrificed. Hematoxylin and eosin analysis, Masson staining and hydroxyproline (Hyp) assessment were performed to observe histopathological changes and collagen deposition. mRNA and protein levels of CXCL14, CXC chemokine receptor 4 (CXCR4), collagen I/III, α‑smooth muscle actin (α‑SMA), MMP2/9 and phosphorylated‑Smad 2/3 in lung tissue were further evaluated. Similar effects in preventing lung damage were observed histopathologically for Dxs and BBR compared with the BLM group. These treatments further reduced levels of Hyp, CXCL14, CXCR4, collagen I/III, MMP2/9, α‑SMA and p‑Smad 2/3. The combination of Dxs and BBR exhibited increased effectiveness compared with the single treatments. Results further suggested that antifibrotic mechanisms were involved in inhibiting CXCL14 and MMP2/MMP9 expression, and preventing the activation of Smad2/3 and hedgehog signaling pathways. The combined use of Dxs and BBR may represent a potential therapeutic approach for PF.

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