Effect of Baofeikang Granule on Pulmonary Fibrosis in Rats by Regulating Wnt/<italic style="font-style: italic">β</italic>-catenin Signaling Pathway

Jia-mei WANG; Xue-feng GONG; Ming-sheng LYU; Dan HOU; Shuai-yang HUANG; Shi-yu ZHANG; Hong-sheng CUI

doi:10.13422/j.cnki.syfjx.20212221

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Effect of Baofeikang Granule on Pulmonary Fibrosis in Rats by Regulating Wnt/β-catenin Signaling Pathway

更新时间：2021-12-14

- Effect of Baofeikang Granule on Pulmonary Fibrosis in Rats by Regulating Wnt/β-catenin Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 2, Pages: 47-54(2022)
- 作者机构：
  
  1.北京中医药大学第三附属医院，北京 100029
  2.北京中医药大学，北京 100029
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20212221
  CLC： R22;R242;R2-031;R285.5
- Published：20 January 2022，
  
  Published Online：28 September 2021，
  
  Received：28 June 2021，
- 稿件说明：
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王佳美,弓雪峰,吕明圣等.保肺康颗粒通过调控Wnt/β-catenin信号通路干预大鼠肺纤维化[J].中国实验方剂学杂志,2022,28(02):47-54.

WANG Jia-mei,GONG Xue-feng,LYU Ming-sheng,et al.Effect of Baofeikang Granule on Pulmonary Fibrosis in Rats by Regulating Wnt/β-catenin Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(02):47-54.
王佳美,弓雪峰,吕明圣等.保肺康颗粒通过调控Wnt/β-catenin信号通路干预大鼠肺纤维化[J].中国实验方剂学杂志,2022,28(02):47-54. DOI： 10.13422/j.cnki.syfjx.20212221.

WANG Jia-mei,GONG Xue-feng,LYU Ming-sheng,et al.Effect of Baofeikang Granule on Pulmonary Fibrosis in Rats by Regulating Wnt/β-catenin Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(02):47-54. DOI： 10.13422/j.cnki.syfjx.20212221.

摘要

目的

基于保肺康颗粒对Wnt/

-连环蛋白（

-catenin）信号通路的影响，探讨其对于肺纤维化大鼠模型的干预作用。

方法

将50只健康大鼠适应性喂养1周后，随机选取8只作为空白组，其余42只大鼠采用常规麻醉后气管内注入硫酸博莱霉素溶液（5 mg·kg

-1

）的方法制备肺纤维化模型，空白组以相同操作方法注入等量生理盐水。造模后第7天，将剩余33只存活的博莱霉素造模大鼠随机剔除1只，其余32只随机分为模型组、醋酸泼尼松组、保肺康低、高剂量组，每组8只。保肺康高、低剂量组分别给予保肺康颗粒27.18，13.59 g·kg

-1

灌胃，醋酸泼尼松组给予醋酸泼尼松片1.17 mg·kg

-1

灌胃，空白组和模型组以等量生理盐水灌胃，每天1次，连续21 d。比较各组大鼠肺顺应性和通气功能、病理学改变和纤维化程度评分、肺组织内Ⅰ型胶原（Col Ⅰ）和血清内羟脯氨酸（HYP）水平及肺组织中Wnt3a，

-catenin蛋白相对表达。

结果

与空白组比较，模型组大鼠肺功能指标用力肺活量（FVC），用力最大呼气流速（PEF），肺总阻力（RL）和动态顺应性（Cydn）均明显下降（

0.05，

0.01），模型组肺组织形态严重毁损，大量连续纤维化灶形成，纤维化严重程度评分显著升高（

0.01），肺组织内Col Ⅰ和血清内HYP水平均显著升高（

0.01），Wnt3a，

-catenin蛋白表达水平均显著升高（

0.01）。与模型组比较，醋酸泼尼松组、保肺康低、高剂量组FVC，PEF，Cydn均明显提高（

0.05，

0.01）；醋酸泼尼松组、保肺康低、高剂量组病理学表现均有所改善，纤维化程度评分低于模型组（

0.05，

0.01），保肺康高、低剂量组评分低于醋酸泼尼松组（

0.01）；醋酸泼尼松组、保肺康低、高剂量组肺组织Col Ⅰ，HYP水平均低于模型组（

0.05，

0.01），保肺康高剂量组Col Ⅰ水平低于醋酸泼尼松组（

0.01），保肺康高、低剂量组血清内HYP的水平均低于醋酸泼尼松组（

0.01）；保肺康高剂量组Wnt3a蛋白表达水平低于模型组（

0.05），醋酸泼尼松组、保肺康低剂量组和保肺康高剂量组

-catenin蛋白表达水平低于模型组（

0.05，

0.01），且保肺康高剂量组表达水平低于醋酸泼尼松组（

0.01）。

结论

保肺康颗粒能够减轻博莱霉素所致大鼠肺纤维化，减少胶原沉积，改善肺顺应性，提高肺通气功能，对Wnt/

-catenin信号通路的抑制可能是其机制之一。

Abstract

Objective

To explore the intervention effect of Baofeikang granule （BFK） on the rat model of pulmonary fibrosis through the Wnt/

-catenin signaling pathway.

Method

After adaptive feeding for one week， 50 healthy rats were randomly divided into a blank group （

=8） and an experimental group （

=42）. After anesthesia， the rats in the experimental group were injected with bleomycin sulfate solution （5 mg·kg

-1

） into the trachea for the induction of the pulmonary fibrosis model. Those in the blank group were injected with the same amount of normal saline under the same manipulation. On the 7

day after modeling， one of the remaining 33 rats alive was randomly removed， and the other 32 model rats were assigned into a model group （

=8）， a prednisone acetate （1.17 mg·kg

-1

） group （

=8）， a low-dose BFK （13.59 g·kg

-1

） group （

=8）， and a high-dose BFK （27.18 g·kg

-1

） group （

=8）. The rats in the groups with drug intervention were treated correspondingly by gavage once per day for 21 days， and those in the blank group and the model group received the same amount of normal saline. The pulmonary compliance and ventilatory function， the scores of pathological changes and fibrosis， the levels of type Ⅰ collagen （Col Ⅰ） in lung tissues and hydroxyproline （HYP） in the serum， and the relative expression of Wnt3a and

-catenin protein in lung tissues were compared.

Result

Compared with the blank group， the model group showed reduced pulmonary function indexes， such as forced vital capacity （FVC）， peak expiratory flow （PEF）， the resistance of lung （RL）， and dynamic compliance （Cdyn）（

0.05，

0.01）， severely damaged lung tissue morphology， massive formed continuous fibrous foci， increased fibrosis score （

0.01）， elevated levels of Col Ⅰ in lung tissues and HYP in the serum （

0.01）， and up-regulated expression of Wnt3a and

-catenin （

0.01）. FVC， PEF， and Cdyn levels in the prednisone acetate group and the BFK groups were higher than those in the model group （

0.05，

0.01）. Pathological changes were improved in the groups with drug intervention， and fibrosis scores were decreased as compared with the model group （

0.05，

0.01）. The scores in the BFK groups were lower than that in the prednisone acetate group （

0.01）. The levels of Col Ⅰ and HYP in the groups with drug intervention were lower than those in the model group （

0.05，

0.01）. The level of Col Ⅰ in the prednisone acetate group was higher than that in the high-dose BFK group （

0.01）. The levels of serum HYP in the BFK groups was lower than that in the prednisone acetate group （

0.01）. The protein expression of Wnt3a in lung tissues of the high-dose BFK group was lower than that of the model group （

0.05）. The protein expression of

-catenin in the prednisone acetate group and the BFK groups was lower than that in the model group （

0.05，

0.01）， and the expression level in the high-dose BFK group was lower than that in the prednisone acetate group （

0.01）.

Conclusion

BFK can relieve bleomycin sulfate-induced pulmonary fibrosis， reduce collagen deposition， improve pulmonary compliance， and enhance pulmonary ventilatory function in rats. One of its mechanisms is presumedly the inhibition of the Wnt/

-catenin signaling pathway.

关键词

保肺康颗粒肺纤维化大鼠Wnt/β-连环蛋白（β-catenin）信号通路胶原沉积

Keywords

Baofeikang granulerats with pulmonary fibrosisWnt/β-catenin signaling pathwaycollagen deposition

references

RAGHU G， COLLARD H R， EGAN J J， et al. An official ATS/ERS/JRS/ALAT statement： idiopathic pulmonary fibrosis： evidence-based guidelines for diagnosis and management［J］. Am J Respir Crit Care Med， 2011，183（6）：788-824.

RAGHU G， ROCHWERG B， ZHANG Y， et al. An official ATS/ERS/JRS/ALAT clinical practice guideline： treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline［J］. Am J Respir Crit Care Med， 2015， 192（5）：e3-e19.

WOLTERS P J， COLLARD H R， JONES K D. Pathogenesis of idiopathic pulmonary fibrosis［J］. Annu Rev Pathol， 2014，9：157-179.

SHI J， LI F， LUO M， et al. Distinct roles of Wnt/β-catenin signaling in the pathogenesis of chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis［J］. Mediators Inflamm， 2017，2017：3520581.

晁恩祥，张纾难. 肺痿再辨识［J］. 北京中医药大学学报， 1997， 20（5）：14-15.

李菊莲，王宇，邓海娟. 肺痹与肺间质纤维化关系探讨［J］. 甘肃科技， 2003（12）：113-114.

武维屏，任传云.肺间质纤维化中医辨治思路［J］.中医杂志，2005，46（2）：139-141.

郭玉洁. 保肺康颗粒提高慢性阻塞性肺疾病合并肺间质纤维化临床疗效评价［D］.北京：北京中医药大学，2019.

李倩男. 保肺康颗粒提高慢性阻塞性肺疾病合并肺间质纤维化临床疗效评价［D］. 北京：北京中医药大学，2016.

王鹤，张广平，侯红平，等.博来霉素不同给药方式致大鼠肺纤维化模型探讨［J］.中国实验方剂学杂，2019，25（11）：73-79.

NAIR A， MORSY M A， JACOB S. Dose translation between laboratory animals and human in preclinical and clinical phases of drug development［J］. Drug Dev Res， 2018，79（8）：373-382.

HUBNER R H， GITTER W， El MOKHTARI N E， et al. Standardized quantification of pulmonary fibrosis in histological samples［J］. Biotechniques， 2008，44（4）：507-517.

KATZEN J， BEERS M F. Contributions of alveolar epithelial cell quality control to pulmonary fibrosis［J］. J Clin Invest， 2020，130（10）：5088-5099.

PARIMON T， YAO C， STRIPP B R， et al. Alveolar epithelial type Ⅱ cells as drivers of lung fibrosis in idiopathic pulmonary fibrosis［J］. Int J Mol Sci， 2020，21（7）：2269.

CHANDA D， OTOUPALOVA E， SMITH S R， et al. Developmental pathways in the pathogenesis of lung fibrosis［J］. Mol Aspects Med， 2019，65：56-69.

宋建平，刘方州，李伟，等.生脉饮对肺纤维化模型大鼠支气管肺泡灌洗液中谷胱甘肽含量的影响［J］.中国中医药科技，2002，doi：TJYY.0.2002-01-005http://dx.doi.org/TJYY.0.2002-01-005.

任春贞，骆亚莉，刘永琦，等.当归防治肺纤维化的研究进展［J］.时珍国医国药，2017，28（1）：199-201.

曾赛丽，游晓星，张秀峰，等.苦参碱减轻博来霉素致大鼠肺纤维化［J］.基础医学与临床，2014，34（4）：504-508.

张心月，李慧，尹亚慧，等.连翘、麦冬对肺纤维化大鼠TIMP-1表达的影响［J］.山东中医药大学学报，2019，43（2）：175-180.

李善华，黄萍，陈琴，等.红景天苷对博莱霉素诱导大鼠肺纤维化后VEGF及MMP表达的影响［J］.实用药物与临床，2016，19（11）：1340-1343.

BASTAKOTY D， YOUNG P P. Wnt/β-catenin pathway in tissue injury： roles in pathology and therapeutic opportunities for regeneration［J］. Faseb J，2016，30（10）：3271-3284.

TZOUVELEKIS A， GOMATOU G， BOUROS E， et al. Common pathogenic mechanisms between idiopathic pulmonary fibrosis and lung cancer［J］. Chest， 2019，156（2）：383-391.

LI X， LIU X， DENG R， et al. Betulinic acid attenuated bleomycin-induced pulmonary fibrosis by effectively intervening Wnt/β-catenin signaling［J］. Phytomedicine， 2021，81：153428.

LI X， LIU X， DENG R， et al. Nintedanib inhibits Wnt3a-induced myofibroblast activation by suppressing the Src/β-catenin pathway［J］. Front Pharmacol， 2020，11：310.

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Effect of Baofeikang Granule on Pulmonary Fibrosis in Rats by Regulating Wnt/β-catenin Signaling Pathway

DOI：10.13422/j.cnki.syfjx.20212221

摘要

Abstract

关键词

Keywords

references