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

Authors：

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;

Corresponding?author：

XIAO Jinling, Email: xmwhrbmu@163.com

Keywords：

Pulmonary fibrosis; Acute exacerbation; Bone marrow mesenchymal stem cells; Diammonium glycyrrhizinate; Transforming growth factor-β1; Oxidative stress

DOI：

10.7507/1671-6205.201902011

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

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 28^th 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

1.	中華醫學會呼吸病學分會間質性肺病學組. 特發性肺纖維化急性加重診斷和治療中國專家共識. 中華醫學雜志, 2019, 99(26): 2014-2023.
2.	雷凱春, 岳紅梅, 周婷婷. 特發性肺纖維化治療新進展. 中國呼吸與危重監護雜志, 2019, 18(2): 199-203.
3.	趙蓉, 呂凌. 甘草酸二銨藥理研究和臨床應用進展. 亞太傳統醫藥, 2008, 4(3): 31-36.
4.	秦剛, 施光峰, 宋艷艷, 等. 甘草酸二銨治療慢性乙型肝炎 3201 例薈萃分析. 中華傳染病雜志, 2005, 23(5): 333-337.
5.	方妮, 周鴻江, 陳俊健. 甘草酸二銨對穩定期慢性阻塞性肺疾病的臨床療效及對患者血清炎性因子和外周血 T 淋巴細胞水平的影響. 中國醫藥, 2019, 14(9): 1326-1330.
6.	李崢, 黃華, 陳鳳坤, 等. 甘草酸二銨與黃芪注射液治療急性肺損傷療效分析. 中國中西醫結合急救雜志, 2013, 20(4): 213-215.
7.	韓美玉, 韓志遠. 甘草酸二銨佐治支氣管哮喘對肺功能、氣道炎癥和免疫功能的影響. 中國藥業, 2018, 27(18): 56-58.
8.	黃坤, 吳曉梅, 王欣燕, 等. 骨髓間充質干細胞向肺泡細胞轉化的實驗研究. 中國呼吸與危重監護雜志, 2011, 10(6): 572-576.
9.	崔璦, 代華平, 戴建武, 等. 骨髓間充質干細胞對博來霉素致大鼠肺纖維化形成的影響. 中華結核和呼吸雜志, 2007, 30(9): 677-682.
10.	Szapiel SV, Elson NA, Fulmer JD, et al. Bleomycin-induced interstitial pulmonary disease in the nude, athymic mouse. Am Rev Respir Dis, 1979, 120(4): 893-899.
11.	Mokhber Dezfouli MR, Sadeghian Chaleshtori S, Moradmand A, et al. Hydrocortisone promotes differentiation of mouse embryonic stem cell-derived definitive endoderm toward lung alveolar epithelial cells. Cell J, 2019, 20(4): 469-476.
12.	中華醫學會呼吸病學分會間質性肺疾病學組. 特發性肺纖維化診斷和治療中國專家共識. 中華結核和呼吸雜志, 2016, 39(6): 427-432.
13.	Yoon HY, Park S, Kim DS, et al. Efficacy and safety of nintedanib in advanced idiopathic pulmonary fibrosis. Respir Res, 2018, 19(1): 203-213.
14.	Varone F, Sgalla G, Lovene B, et al. Nintedanib for the treatment of idiopathic pulmonary fibrosis. Expert Opin Pharmacother, 2018, 19(2): 167-175.
15.	Tepede A, Yogaratnam D. Nintedanib for idiopathic pulmonary fibrosis. J Pharm Pract, 2019, 32(2): 199-206.
16.	Kumar A, Kapnadak SG, Girgis RE, et al. Lung transplantation in idiopathic pulmonary fibrosis. Expert Rev Respir Med, 2018, 12(5): 375-385.
17.	金曉光, 代華平, 龐寶森, 等. 博來霉素致大鼠肺纖維化模型肺組織的動態病理變化及其發生機制. 中國病理生理雜志, 2009, 25(4): 708-714.
18.	柴文戍, 李永春, 劉玉玲, 等. 博來霉素致肺纖維化大鼠形態學變化的實驗研究. 中國實驗動物學報, 2003, 11(2): 77-80.
19.	Demkow U. Immunopathogenesis of idiopathic pulmonary fibrosis. Pneumonol Alergol Pol, 2014, 82(1): 55-60.
20.	黃坤, 吳曉梅, 王欣燕, 等. 骨髓間充質干細胞移植對大鼠肺纖維化的影響. 中華結核和呼吸雜志, 2012, 35(9): 659-664.
21.	Kr?henbühl S, Hasler F, Frey BM, et al. Kinetics and dynamics of orally administered 18 beta-glycyrrhetinic acid in humans. J Clin Endocrinol Metab, 1994, 78(3): 581-585.
22.	Asl MN, Hosseinzadeh H. Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother Res, 2008, 22(6): 709-724.
23.	Li Y, Liu TY, Yan C, et al. Diammonium glycyrrhizinate protects against nonalcoholic fatty liver disease in mice through modulation of gut microbiota and restoration of intestinal barrier. Mol Pharm, 2018, 15(9): 3860-3870.
24.	Zhao X, Liu J, Yang S, et al. Diammonium glycyrrhizinate alleviates hepatopulmonary syndrome via restoring superoxide dismutase 3 activity in rats. Eur J Pharmacol, 2017, 15(7): 144-150.

1. 中華醫學會呼吸病學分會間質性肺病學組. 特發性肺纖維化急性加重診斷和治療中國專家共識. 中華醫學雜志, 2019, 99(26): 2014-2023.
2. 雷凱春, 岳紅梅, 周婷婷. 特發性肺纖維化治療新進展. 中國呼吸與危重監護雜志, 2019, 18(2): 199-203.
3. 趙蓉, 呂凌. 甘草酸二銨藥理研究和臨床應用進展. 亞太傳統醫藥, 2008, 4(3): 31-36.
4. 秦剛, 施光峰, 宋艷艷, 等. 甘草酸二銨治療慢性乙型肝炎 3201 例薈萃分析. 中華傳染病雜志, 2005, 23(5): 333-337.
5. 方妮, 周鴻江, 陳俊健. 甘草酸二銨對穩定期慢性阻塞性肺疾病的臨床療效及對患者血清炎性因子和外周血 T 淋巴細胞水平的影響. 中國醫藥, 2019, 14(9): 1326-1330.
6. 李崢, 黃華, 陳鳳坤, 等. 甘草酸二銨與黃芪注射液治療急性肺損傷療效分析. 中國中西醫結合急救雜志, 2013, 20(4): 213-215.
7. 韓美玉, 韓志遠. 甘草酸二銨佐治支氣管哮喘對肺功能、氣道炎癥和免疫功能的影響. 中國藥業, 2018, 27(18): 56-58.
8. 黃坤, 吳曉梅, 王欣燕, 等. 骨髓間充質干細胞向肺泡細胞轉化的實驗研究. 中國呼吸與危重監護雜志, 2011, 10(6): 572-576.
9. 崔璦, 代華平, 戴建武, 等. 骨髓間充質干細胞對博來霉素致大鼠肺纖維化形成的影響. 中華結核和呼吸雜志, 2007, 30(9): 677-682.
10. Szapiel SV, Elson NA, Fulmer JD, et al. Bleomycin-induced interstitial pulmonary disease in the nude, athymic mouse. Am Rev Respir Dis, 1979, 120(4): 893-899.
11. Mokhber Dezfouli MR, Sadeghian Chaleshtori S, Moradmand A, et al. Hydrocortisone promotes differentiation of mouse embryonic stem cell-derived definitive endoderm toward lung alveolar epithelial cells. Cell J, 2019, 20(4): 469-476.
12. 中華醫學會呼吸病學分會間質性肺疾病學組. 特發性肺纖維化診斷和治療中國專家共識. 中華結核和呼吸雜志, 2016, 39(6): 427-432.
13. Yoon HY, Park S, Kim DS, et al. Efficacy and safety of nintedanib in advanced idiopathic pulmonary fibrosis. Respir Res, 2018, 19(1): 203-213.
14. Varone F, Sgalla G, Lovene B, et al. Nintedanib for the treatment of idiopathic pulmonary fibrosis. Expert Opin Pharmacother, 2018, 19(2): 167-175.
15. Tepede A, Yogaratnam D. Nintedanib for idiopathic pulmonary fibrosis. J Pharm Pract, 2019, 32(2): 199-206.
16. Kumar A, Kapnadak SG, Girgis RE, et al. Lung transplantation in idiopathic pulmonary fibrosis. Expert Rev Respir Med, 2018, 12(5): 375-385.
17. 金曉光, 代華平, 龐寶森, 等. 博來霉素致大鼠肺纖維化模型肺組織的動態病理變化及其發生機制. 中國病理生理雜志, 2009, 25(4): 708-714.
18. 柴文戍, 李永春, 劉玉玲, 等. 博來霉素致肺纖維化大鼠形態學變化的實驗研究. 中國實驗動物學報, 2003, 11(2): 77-80.
19. Demkow U. Immunopathogenesis of idiopathic pulmonary fibrosis. Pneumonol Alergol Pol, 2014, 82(1): 55-60.
20. 黃坤, 吳曉梅, 王欣燕, 等. 骨髓間充質干細胞移植對大鼠肺纖維化的影響. 中華結核和呼吸雜志, 2012, 35(9): 659-664.
21. Kr?henbühl S, Hasler F, Frey BM, et al. Kinetics and dynamics of orally administered 18 beta-glycyrrhetinic acid in humans. J Clin Endocrinol Metab, 1994, 78(3): 581-585.
22. Asl MN, Hosseinzadeh H. Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother Res, 2008, 22(6): 709-724.
23. Li Y, Liu TY, Yan C, et al. Diammonium glycyrrhizinate protects against nonalcoholic fatty liver disease in mice through modulation of gut microbiota and restoration of intestinal barrier. Mol Pharm, 2018, 15(9): 3860-3870.
24. Zhao X, Liu J, Yang S, et al. Diammonium glycyrrhizinate alleviates hepatopulmonary syndrome via restoring superoxide dismutase 3 activity in rats. Eur J Pharmacol, 2017, 15(7): 144-150.

Previous Article
Clinical analysis of 15 cases of idiopathic hypereosinophilic syndrome
Next Article
肉芽腫性多血管炎致中樞性尿崩癥一例并文獻復習

Chinese Journal of Respiratory and Critical Care Medicine

Study on the treatment of acute exacerbation of pulmonary fibrosis in rats by diammonium glycyrrhizinate combined with bone marrow mesenchymal stem cells

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content