HUANG Kun 1 , ZHOU Yong 2 , LIU Meifang 1 , WANG Xinyan 1 , KANG Xiaowen 1 , XIAO Jinling 1
  • 1. Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P. R. China;
  • 2. Department of Respiratory and Critical Care Medicine, People’s Hospital of Aletai Region, Aletai, Xinjiang 836500, P. R. China;
XIAO Jinling, Email: xmwhrbmu@163.com
Pulmonary fibrosis; Acute exacerbation; Bone marrow mesenchymal stem cells; Diammonium glycyrrhizinate; Transforming growth factor-β1; Oxidative stress
10.7507/1671-6205.201902011
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Objective To investigate the effect of diammonium glycyrrhizinate (DG) plus bone marrow mesenchymal stem cells (MSCs) transplantation in the treatment of acute exacerbation of pulmonary fibrosis induced by bleomycin (BLM) in rats.Methods MSCs were isolated from male Wistar rats and cultured in vitro. Twenty-four female Wistar rats were randomly divided into 4 groups. The NC group was intratracheally injected with normal saline; the BLM group, the MSC group and the DGMSC group were intratracheally injected with BLM for 7 days; then the MSC group was injected with 0.5 mL of MSCs solution (2.5×106 cells) into the tail vein; the DGMSC group was intraperitoneally injected with DG for 21 days in a dose of 150 mg·kg–1·d–1 on the base of the MSCs injection. The rats were sacrificed on the 28th day and the lung tissue was extracted. Pathological examination was performed to determine the degree of alveolitis and pulmonary fibrosis. Immunofluorescence was used to detect the number and distribution of alveolar type Ⅱ epithelial cells. Alkali hydrolysis method was used to determine the content of hydroxyproline (HYP) in lung tissue; thiobarbituric acid method was used to measure the content of malondialdehyde (MDA) in lung tissue; colorimetric method was used to determine the superoxide dismutase activity (SOD) and total antioxidant capacity (T-AOC); enzyme linked immunosorbent assay was used to detect the expression levels of tumor necrosis factor-α (TNF-α ) and transforming growth factor-β1 (TGF-β1) in lung tissue homogenates.Results The DG combined with MSCs injection can reduce the degree of alveolitis and pulmonary fibrosis in BLM model rats. The content of HYP and TGF-β1 in lung tissue homogenate of the DGMSC group were significantly lower than those in the MSC group (P<0.05). Meanwhile, DG combined with MSCs injection significantly increased the antioxidant capacity of the BLM model rats. MDA content decreased, SOD activity and T-AOC ability improved significantly in the DGMSC group compared with the MSC group (P<0.05). The alveolar type Ⅱ epithelial cells were significantly increased and the cell morphology was maintained in the DGMSC group compared with the MSC group.Conclusions DG has a synergistic effect with MSCs in treatment of acute exacerbation of pulmonary fibrosis. The mechanism may be related to reducing inflammatory factors during pulmonary fibrosis, attenuating oxidative stress and promoting MSCs migration into lung tissue and transformation to alveolar type Ⅱ epithelial cells.

Citation： HUANG Kun, ZHOU Yong, LIU Meifang, WANG Xinyan, KANG Xiaowen, XIAO Jinling. Study on the treatment of acute exacerbation of pulmonary fibrosis in rats by diammonium glycyrrhizinate combined with bone marrow mesenchymal stem cells. Chinese Journal of Respiratory and Critical Care Medicine, 2020, 19(1): 64-69. doi: 10.7507/1671-6205.201902011 Copy

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