|
|
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 |
|
|
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.
|
Received: 18 July 2021
Published: 17 May 2022
|
|
Corresponding Authors:
HUANG Ping
E-mail: huangping@hmc.edu.cn
|
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
|
|
[1] |
中华医学会呼吸病学分会. 特发性肺(间质)纤维化诊断和治疗指南(草案)[J]. 中华结核和呼吸杂志, 2002, 25(7): 387-389 Respiratory Society of Chinese Medical Association. Guidelines for diagnosis and treatment of idiopathic pulmonary (interstitial) fibrosis (draft)[J]. Chinese Journal of Tuberculosis and Respiratory Diseases, 2002, 25(7): 387-389. (in Chinese)
|
|
|
[2] |
沈沁雪, 彭 红. 特发性肺纤维化病情的临床评估[J]. 中南大学学报(医学版), 2021, 46(3): 309-315 SHEN Qinxue, PENG Hong. Clinical evaluation on idiopathic pulmonary fibrosis[J]. Journal of Central South University (Medical Science), 2021, 46(3): 309-315. (in Chinese)
|
|
|
[3] |
MARTINEZF J, YOWE, FLAHERTYK R, et al.Effect of antimicrobial therapy on respiratory hospitalization or death in adults with idiopathic pulmonary fibrosis[J]JAMA, 2021, 325( 18): 1841.
doi: 10.1001/jama.2021.4956
|
|
|
[4] |
DUCKWORTHA, GIBBONSM A, ALLENR J, et al.Telomere length and risk of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease: a mendelian randomisation study[J]Lancet Respiratory Med, 2021, 9( 3): 285-294.
doi: 10.1016/S2213-2600(20)30364-7
|
|
|
[5] |
GHUMMANM, DHAMECHAD, GONSALVESA, et al.Emerging drug delivery strategies for idiopathic pulmonary fibrosis treatment[J]Eur J Pharm Biopharm, 2021, 1-12.
doi: 10.1016/j.ejpb.2021.03.017
|
|
|
[6] |
LANCASTERL H, DE ANDRADEJ A, ZIBRAKJ D, et al.Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis[J]Eur Respir Rev, 2017, 26( 146): 170057.
doi: 10.1183/16000617.0057-2017
|
|
|
[7] |
WONGKARNJANAA, YANAGIHARAT, KOLBM R. Treatment of idiopathic pulmonary fibrosis with Nintedanib: an update[J]Expert Rev Respiratory Med, 2019, 13( 12): 1139-1146.
doi: 10.1080/17476348.2019.1673733
|
|
|
[8] |
RODRÍGUEZ-PORTALJ A. Efficacy and safety of nintedanib for the treatment of idiopathic pulmonary fibrosis: an update[J]Drugs R D, 2018, 18( 1): 19-25.
doi: 10.1007/s40268-017-0221-9
|
|
|
[9] |
LIS, YANGX, LIW, et al.N-acetylcysteine downregulation of lysyl oxidase activity alleviating bleomycin-induced pulmonary fibrosis in rats[J]Respiration, 2012, 84( 6): 509-517.
doi: 10.1159/000340041
|
|
|
[10] |
王彦君, 王雪林, 李欣泽, 等. 中医药治疗特发性肺纤维化研究[J]. 中国中医基础医学杂志, 2021, 27(6):1033-1035 WANG Yanjun, WANG Xuelin, LI Xinze, et al. Study on the treatment of idiopathic pulmonary fibrosis with traditional Chinese medicine[J].Chinese Journal of Basic Medicine in Traditional Chinese Medicine, 2021, 27(6): 1033-1035. (in Chinese)
|
|
|
[11] |
吕 凌, 袁 佺, 王彩霞. 特发性肺纤维化从脾论治思路探讨[J]. 中国中医基础医学杂志, 2016, 22(7): 937-938 LYU Ling, YUAN Tong, WANG Caixia. Discussion on idiopathic pulmonary fibrosis from spleen treatment[J]. Chinese Journal of Basic Medicine in Traditional Chinese Medicine, 2016, 22(7): 937-938. (in Chinese)
|
|
|
[12] |
郑 钰, 吕晓东, 庞立健, 等. 中医药治疗特发性肺纤维化临床研究方法初探[J]. 辽宁中医药大学学报, 2019, 21(11): 102-105 ZHENG Yu, LYU Xiaodong, PANG Lijian, et al. Preliminary study on clinical research methods of Chinese medicine in the treatment of idiopathic pulmonary fibrosis[J]. Journal of Liaoning University of Traditional Chinese Medicine, 2019, 21(11): 102-105. (in Chinese)
|
|
|
[13] |
周俐斐, 芦柏震, 陈峰阳, 等. 清肺合剂的清除自由基和抗氧化作用[J]. 中草药, 2015(37): 2527-2530 ZHOU Lifei, LU Bozhen, CHEN Fengyang, et al. Free radical scavenging and antioxidant effect of Qingfei Mixture[J]. Chinese Traditional Patent Medicine, 2015(37): 2527-2530. (in Chinese)
|
|
|
[14] |
王跃珍, 崔 巍, 王 准, 等. 中肺合剂对血浆 TGF-β和 IL-6 影响及防治放射性肺炎的临床观察[J].中华中医药学刊, 2012, 30(7): 1541-1544 WANG Yuezhen, CUI Wei, WANG Zhun, et al. Clinical study of Zhongfei decoction influence on changes of TGF-β and IL-6 and the preventive effects of on radiation-induced pneumonia[J]. Chinese Archives of Traditional Chinese Medicine, 2012, 30(7): 1541-1544. (in Chinese)
|
|
|
[15] |
TORLAKOVICE E, NIELSENS, FRANCISG, et al.Standardization of positive controls in diagnostic immunohistochemistry[J]Appl Immunohistochem Mol Morphol, 2015, 23( 1): 1-18.
doi: 10.1097/PAI.0000000000000163
|
|
|
[16] |
MACKINNONA C, GIBBONSM A, FARNWORTHS L, et al.Regulation of transforming growth factor-β1-driven lung fibrosis by galectin-3[J]Am J Respir Crit Care Med, 2012, 185( 5): 537-546.
doi: 10.1164/rccm.201106-0965OC
|
|
|
[17] |
ORNATOWSKIW, LUQ, YEGAMBARAMM, et al.Complex interplay between autophagy and oxidative stress in the development of pulmonary disease[J]Redox Biol, 2020, 101679.
doi: 10.1016/j.redox.2020.101679
|
|
|
[18] |
VEITHC, BOOTSA W, IDRISM, et al.Redox imbalance in idiopathic pulmonary fibrosis: a role for oxidant cross-talk between NADPH oxidase enzymes and mitochondria[J]Antioxid Redox Signal, 2019, 31( 14): 1092-1115.
doi: 10.1089/ars.2019.7742
|
|
|
[19] |
OTOUPALOVA E, SMITH S, CHENG G, et al. Oxidative stress in pulmonary fibrosis[J]. Compr Physiol, 2020, 10(2): 509-547
|
|
|
[20] |
DIAZK T, SKARIAS, HARRISK, et al.Delivery and safety of inhaled interferon-γ in idiopathic pulmonary fibrosis[J]J Aerosol Med Pulmonary Drug Deliver, 2012, 25( 2): 79-87.
doi: 10.1089/jamp.2011.0919
|
|
|
[21] |
LEE J, ARISI I, PUXEDDU E, et al. Bronchoalveolar lavage (BAL) cells in idiopathic pulmonary fibrosis express a complex pro-inflammatory, pro-repair, angiogenic activation pattern, likely associated with macrophage iron accumulation[J/OL]. PLoS One, 2018, 13(4): e0194803
|
|
|
[22] |
BURMANA, KROPSKIJ A, CALVIC L, et al.Localized hypoxia links ER stress to lung fibrosis through induction of C/EBP homologous protein[J/OL]JCI Insight, 2018, 3( 16): e99543.
doi: 10.1172/jci.insight.99543
|
|
|
[23] |
KNOBLOCHJ, LINY, KONRADIJ, et al.Inflammatory responses of airway smooth muscle cells and effects of endothelin receptor antagonism[J]Am J Respir Cell Mol Biol, 2013, 49( 1): 114-127.
doi: 10.1165/rcmb.2012-0287OC
|
|
|
[24] |
ZHUY, TANJ, XIEH, et al.HIF‐1α regulates EMT via the Snail and β‐catenin pathways in paraquat poisoning‐induced early pulmonary fibrosis[J]J Cell Mol Med, 2016, 20( 4): 688-697.
doi: 10.1111/jcmm.12769
|
|
|
[25] |
PHILIPK, MILLST W, DAVIESJ, et al.HIF1A up‐regulates the ADORA2B receptor on alternatively activated macrophages and contributes to pulmonary fibrosis[J]Faseb J, 2017, 31( 11): 4745-4758.
doi: 10.1096/fj.201700219R
|
|
|
[26] |
ZHANGY, LUW, ZHANGX, et al.Cryptotanshinone protects against pulmonary fibrosis through inhibiting Smad and STAT3 signaling pathways[J]Pharmacol Res, 2019, 104307.
doi: 10.1016/j.phrs.2019.104307
|
|
|
[27] |
SHOCHETG E, BROOKE, BARDENSTEIN-WALDB, et al.Integrin alpha-5 silencing leads to myofibroblastic differentiation in IPF-derived human lung fibroblasts[J]Therapeutic Adv Chronic Dis, 2020, 204062232093602.
doi: 10.1177/2040622320936023
|
|
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
|
Shared |
|
|
|
|
|
Discussed |
|
|
|
|