Effect and Mechanism of Xiao Qinglongtang Against Right Ventricular Dysfunction in Rats with Pulmonary Arterial Hypertension Induced by Monocrotaline

QI Lei; ZHANG Huifei; GONG Ling; HE Jifu; CHEN Wenjing; NIU Weipin; LI Xiao; JIANG Yuehua

doi:10.13422/j.cnki.syfjx.20252101

您当前的位置：

首页 >

文章列表页 >

Effect and Mechanism of Xiao Qinglongtang Against Right Ventricular Dysfunction in Rats with Pulmonary Arterial Hypertension Induced by Monocrotaline

更新时间：2026-01-23

- Effect and Mechanism of Xiao Qinglongtang Against Right Ventricular Dysfunction in Rats with Pulmonary Arterial Hypertension Induced by Monocrotaline
  增强出版
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 32, Issue 4, Pages: 11-19(2026)
- 作者机构：
  
  1.山东中医药大学附属医院，济南 250014
  2.山东中医药大学，济南 250355
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20252101
  CLC： R289;R259;R285
- Received：09 June 2025，
  
  Revised：2025-02-18，
  
  Accepted：28 February 2025，
  
  Published Online：24 September 2025，
  
  Published：20 February 2026
- 稿件说明：
移动端阅览
祁磊,张慧菲,龚玲等.小青龙汤对野百合碱诱导肺动脉高压大鼠右心功能的影响及机制[J].中国实验方剂学杂志,2026,32(04):11-19.

QI Lei,ZHANG Huifei,GONG Ling,et al.Effect and Mechanism of Xiao Qinglongtang Against Right Ventricular Dysfunction in Rats with Pulmonary Arterial Hypertension Induced by Monocrotaline[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(04):11-19.
祁磊,张慧菲,龚玲等.小青龙汤对野百合碱诱导肺动脉高压大鼠右心功能的影响及机制[J].中国实验方剂学杂志,2026,32(04):11-19. DOI： 10.13422/j.cnki.syfjx.20252101.

QI Lei,ZHANG Huifei,GONG Ling,et al.Effect and Mechanism of Xiao Qinglongtang Against Right Ventricular Dysfunction in Rats with Pulmonary Arterial Hypertension Induced by Monocrotaline[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(04):11-19. DOI： 10.13422/j.cnki.syfjx.20252101.

摘要

目的

本研究拟通过建立野百合碱（MCT）诱导的肺动脉高压（PAH）大鼠模型，系统评估小青龙汤对模型大鼠右心功能的保护效应，并进一步揭示其调控右心功能的作用机制。

方法

60只雄性SD大鼠随机分为正常组，模型组，小青龙汤低、中、高剂量（XQLT-L、XQLT-M、XQLT-H）组和贝前列素钠片（BST）组，除正常组外，其余各组大鼠使用MCT（60 mg·kg

-1

）单次皮下注射诱导PAH模型，注射3周后，XQLT-L/M/H组分别灌胃小青龙汤3.07、6.14、12.28 g·kg

-1

·d

-1

，BST组灌胃贝前列素钠12.6 μg·kg

-1

·d

-1

，模型组灌胃等量生理盐水，共给药3周。右心导管插管法检测右心室收缩压（RVSP）；超声心动图评价心功能；右心室组织称质量计算右心室肥厚指数（RVHI）；苏木素-伊红（HE）染色、马松（Masson）染色、透射电镜观察心脏组织形态；超高效液相色谱-串联质谱法（UPLC-MS/MS）分析血清代谢组变化；数据非依赖采集蛋白质组学检测右心室差异蛋白，蛋白免疫印迹法（Western blot）检测解偶联蛋白3（UCP3）、磷酸肌醇3-激酶

催化亚基p110

（PIK3CA）、L1细胞黏附分子（L1CAM）、醌氧化还原酶（CRYZ）蛋白表达；UPLC-MS/MS分析小青龙汤的药物组成成分。

结果

与正常组比较，模型组大鼠RVSP和右心肥厚指数（RVHI）明显升高（

0.05），心肌组织形态出现病理性改变；与模型组比较，各给药组RVSP和RVHI不同程度降低、心功能和心肌组织形态显著改善，小青龙汤各给药组中，XQLT-M组药效最佳（

0.05），与BST组接近。血清代谢组结果显示，与模型组比较，小青龙汤组出现105个差异代谢物［变量重要性投影（VIP）值

1且

0.05］，其中58个升高，47个降低，京都基因与基因组百科全书（KEGG）数据库富集提示，小青龙汤的干预导致苯丙氨酸代谢下调（

0.01），而不饱和脂肪酸生物合成上调（

0.05）。蛋白质组学结果显示，与正常组比较，MCT诱导右心室出现982个差异蛋白，其中455个蛋白上调、527个蛋白下调（|差异倍数（FC）|

1.3，

0.05）；与模型组比较，小青龙汤组出现237个蛋白差异表达，其中124个蛋白上调，113个蛋白下调，二者有57个共有差异蛋白，KEGG富集提示，小青龙汤主要参与矿物质吸收、核糖体生物发生、过氧化物酶体、糖酵解/糖异生、剪接体、甲状腺激素信号通路等调节。Western blot显示与模型组比较，小青龙汤组UCP3、PIK3CA、L1CAM蛋白表达上调，CRYZ蛋白表达下调（

0.05）。

结论

小青龙汤对MCT诱导PAH大鼠具有右心功能保护作用，其机制与维持心肌稳态、减轻右心室重构有关。

Abstract

Objective

This study aimed to establish a monocrotaline （MCT）-induced pulmonary arterial hypertension （PAH） rat model to systematically evaluate the protective effect of Xiao Qinglongtang （XQLT） on right cardiac function in model rats and further elucidate the underlying regulatory mechanism.

Methods

Sixty male SD rats were randomly assigned to the normal group， model group， XQLT low-， medium-， and high-dose groups （XQLT-L/M/H）， and the beraprost sodium tablet group （BST）. Except for the normal group， rats in all other groups were given a single subcutaneous injection of MCT （60 mg·kg

-1

） to induce PAH. Three weeks after injection， rats in the XQLT-L/M/H groups were administered XQLT intragastrically at 3.07， 6.14， 12.28 g·kg

-1

·d

-1

， respectively. Rats in the BST group received beraprost sodium at 12.6 μg·kg

-1

·d

-1

， and rats in the model group received an equal volume of saline. All treatments lasted for 3 weeks. Right ventricular systolic pressure （RVSP） was measured by right ventricular catheterization. Cardiac function was assessed by echocardiography. The right ventricle was weighed to calculate the right ventricular hypertrophy index （RVHI）. Hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy were used to observe myocardial morphology. Serum metabolomic changes were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）. Data-independent acquisition （DIA） proteomics was used to detect differentially expressed （DE） proteins in the right ventricle， and Western blot was used to measure the expression of uncoupling protein 3 （UCP3）， phosphatidylinositol 3-kinase catalytic subunit p110

（PIK3CA）， L1 cell adhesion molecule （L1CAM）， and quinone oxidoreductase （CRYZ）. UPLC-MS/MS was used to analyze the chemical components of XQLT.

Results

Compared with the normal group， the model group showed significantly increased RVSP and RVHI （

0.05）， along with pathological changes in myocardial morphology. Compared with the model group， all XQLT-treated gr

oups exhibited reductions in RVSP and RVHI as well as significant improvements in cardiac function and myocardial morphology. Among the XQLT groups， XQLT-M showed the most pronounced effects （

0.05）， comparable to the BST group. Serum metabolomics revealed 105 differential metabolites in the XQLT groups versus the model group ［variable importance in projection （VIP）

1，

0.05］， including 58 upregulated and 47 downregulated metabolites. KEGG enrichment analysis indicated that XQLT intervention downregulated phenylalanine metabolism （

0.01） and upregulated unsaturated fatty acid biosynthesis （

0.05）. Proteomics analysis showed that 982 DE proteins were identified in the MCT groups versus the normal group， including 455 upregulated and 527 downregulated proteins （|fold change （FC）|

1.3，

0.05）. Compared with the model group， 237 DE proteins were identified in the XQLT groups， including 124 upregulated and 113 downregulated proteins （|FC|

1.3，

0.05）， with 57 overlapping DE proteins. KEGG enrichment suggested that XQLT mainly modulated pathways related to mineral absorption， ribosomal biogenesis， peroxisomes， glycolysis/gluconeogenesis， spliceosomes， and thyroid hormone signaling. Western blot analysis showed that， compared with the model group， XQLT increased the expression of UCP3， PIK3CA， and L1CAM， while decreasing the expression of CRYZ （

0.05）.

Conclusion

XQLT exerts a protective effect on right heart function in MCT-induced PAH rats， and its mechanism is associated with maintaining myocardial homeostasis and alleviating right ventricular remodeling.

关键词

Keywords

references

KOVACS G ， BARTOLOME S ， DENTON P C ， et al . Definition，classification and diagnosis of pulmonary hypertension ［J］. Eur Respir J ， 2024 ， 64 （ 4 ）： 2401324 .

VONK-NOORDEGRAAF A ， HADDAD F ， CHIN K M et al . Right heart adaptation to pulmonary arterial hypertension：Physiology and pathobiology ［J］. J Am Coll Cardiol ， 2013 ， 62 （ 25 Suppl ）： D22 - D33 .

SANTOS-GOMES J ， GANDRA I ， ADAO R ， et al . An overview of circulating pulmonary arterial hypertension biomarkers ［J］. Front Cardiovasc Med ， 2022 ， 9 ： 924873 .

RUOPP N F ， COCKRILL B A . Diagnosis and treatment of pulmonary arterial hypertension：A review ［J］. JAMA ， 2022 ， 327 （ 14 ）： 1379 - 1391 .

GALIE N ， OLSCHEWSKI H ， OUDIZ R J ， et al . Ambrisentan for the treatment of pulmonary arterial hypertension：Results of the ambrisentan in pulmonary arterial hypertension，randomized，double-blind，placebo-controlled，multicenter，efficacy （ARIES） study 1 and 2 ［J］. Circulation ， 2008 ， 117 （ 23 ）： 3010 - 3019 .

LAN N S H ， MASSAM B D ， KULKAMI S S ， et al . Pulmonary arterial hypertension：Pathophysiology and treatment ［J］. Diseases ， 2018 ， 6 （ 2 ）： 38 .

韩福健 . 小青龙汤联合前列地尔治疗慢性肺源性心脏病的疗效分析［J］. 实用中西医结合临床， 2021 ， 21 （ 5 ）： 54 - 55 .

HAN F J . Efficacy analysis of Xiaoqinglong decoction combined with alprostanil in the treatment of chronic pulmonary heart disease ［J］. Pract Clin J Integr Tradit Chin West Med ， 2021 ， 21 （ 5 ）： 54 - 55 .

向燕 . 变通小青龙汤对肺心病患者血清炎症因子水平及心肺功能的影响［J］. 四川中医， 2017 ， 35 （ 11 ）： 80 - 83 .

XIANG Y . Effect of modified Xiaoqinglong decoction on serum inflammatory factors levels and cardiopulmonary function for patients with pulmonary heart disease ［J］. J Sichuan Tradit Chin Med ， 2017 ， 35 （ 11 ）： 80 - 83 .

李兆钰，王永成，周国锋，等 . 小青龙汤治疗寒痰阻肺型慢性心力衰竭的临床疗效及作用机制［J］. 中国实验方剂学杂志， 2021 ， 27 （ 1 ）： 17 - 22 .

LI Z Y ， WANG Y C ， ZHOU G F ， et al . Clinical efficacy and mechanism of Xiaoqinglong decoction in treating chronic heart failure with cold phlegm in lung ［J］. Chin J Exp Tradit Med Form ， 2021 ， 27 （ 1 ）： 17 - 22 .

LI Z Y ， WANG Y C ， JIANG Y H ， et al . Xiao-Qing-Long-Tang maintains cardiac function during heart failure with reduced ejection fraction in salt-sensitive rats by regulating the imbalance of cardiac sympathetic innervation ［J］. Evid Based Complement Alternat Med ， 2020 ， doi： 10.1155/2020/9467271 http://dx.doi.org/10.1155/2020/9467271 .

ZHOU G F ， JIANG Y H ， MA D F ， et al . Xiao-Qing-Long Tang prevents cardiomyocyte hypertrophy，fibrosis，and the development of heart failure with preserved ejection faction in rats by modulating the composition of the gut microbiota ［J］. Biomed Res Int ， 2019 ， doi： 10.1155/2019/9637479 http://dx.doi.org/10.1155/2019/9637479 .

HEATH D ， KAY J M . Medical thickness of pulmonary trunk in rats with cor pulmonale induced by ingestion of Crotalaria spectabilis seeds ［J］. Cardiovasc Res ， 1967 ， 1 （ 1 ）： 74 - 79 .

SMITH P ， KAY J M ， HEATH D . Hypertensive pulmonary vascular disease in rats after prolonged feeding with Crotalaria spectabilis seeds ［J］. J Pathol ， 1970 ， 102 （ 2 ）： 97 - 106 .

BOUCHERAT O ， AGRAWAL V ， LAWRIE A ， et al . The latest in animal models of pulmonary hypertension and right ventricular failure ［J］. Circ Res ， 2022 ， 130 （ 9 ）： 1466 - 1486 .

VAN DE VEERDONK M C ， BOGAARD H J ， VOELKEL N F . The right ventricle and pulmonary hypertension ［J］. Heart Fail Rev ， 2016 ， 21 （ 3 ）： 259 - 271 .

OMURA J ， HABBOUT K ， SHIMAUCHI T ， et al . Identification of long noncoding RNA H19 as a new biomarker and therapeutic target in right ventricular failure in pulmonary arterial hypertension ［J］. Circulation ， 2020 ， 142 （ 15 ）： 1464 - 1484 .

PADANG R ， CHANDRASHEKAR N ， INDRABHINDUWAT M ， et al . Aetiology and outcomes of severe right ventricular dysfunction ［J］. Eur Heart J ， 2020 ， 41 （ 12 ）： 1273 - 1282 .

NOVELLI D ， FUMAGALLI F ， STASZEWSKY L ， et al . Primary pulmonary arterial hypertension：Protocol to assess comprehensively in the rat the response to pharmacologic treatments ［J］. MethodsX ， 2019 ， 7 ： 100771 .

D'ALTO M ， DI MAIO M ， ARGIENTO P ， et al . Right heart failure as a cause of pulmonary congestion in pulmonary arterial hypertension ［J］. Eur J Heart Fail ， 2024 ， 26 （ 4 ）： 817 - 824 .

LYU D M ， CAO X L ， ZHONG L ， et al . Targeting phenylpyruvate restrains excessive NLRP3 inflammasome activation and pathological inflammation in diabetic wound healing ［J］. Cell Rep Med ， 2023 ， 4 （ 8 ）： 101129 .

CZIBIK G ， MEZDARI Z ， MURAT ALTINTAS D ， et al . Dysregulated phenylalanine catabolism plays a key role in the trajectory of cardiac aging ［J］. Circulation ， 2021 ， 144 （ 7 ）： 559 - 574 .

STRYECK S ， GASTRAGER M ， DEGORICIJA V ， et al . Serum concentrations of citrate，tyrosine，2- and 3- hydroxybutyrate are associated with increased 3-month mortality in acute heart failure patients ［J］. Sci Rep ， 2019 ， 9 （ 1 ）： 6743 .

OPPEDISANO F ， MOLLACE R ， TAVERNESE A ， et al . PUFA supplementation and heart failure：Effects on fibrosis and cardiac remodeling ［J］. Nutrients ， 2021 ， 13 （ 9 ）： 2965 .

BLOCK R C ， LIU L X ， HERRINGTON D M ， et al . Predicting risk for incident heart failure with omega-3 fatty acids：From MESA ［J］. JACC Heart Fail ， 2019 ， 7 （ 8 ）： 651 - 661 .

LI H ， DUAN Y T ， CHEN B F ， et al . New pharmacological treatments for heart failure with reduced ejection fraction （HFrEF）：A Bayesian network Meta-analysis ［J］. Medicine （Baltimore）， 2020 ， 99 （ 5 ）： e18341 .

COSTFORD S R ， CHAUDHRY S N ， CRAWFORD S A ， et al . Long-term high-fat feeding induces greater fat storage in mice lacking UCP3 ［J］. Am J Physiol Endocrinol Metab ， 2008 ， 295 （ 5 ）： E1018 - E1024 .

LANG H M ， XIANG Y ， AI Z H ， et al . UCP3 ablation exacerbates high-salt induced cardiac hypertrophy and cardiac dysfunction ［J］. Cell Physiol Biochem ， 2018 ， 46 （ 4 ）： 1683 - 1692 .

HARMANCEY R ， HAIGHT D L ， WATTS K A ， et al . Chronic hyperinsulinemia causes selective insulin resistance and down-regulates uncoupling protein 3 （UCP3） through the activation of sterol regulatory element-binding protein （SREBP）-1 transcription factor in the mouse heart ［J］. J Biol Chem ， 2015 ， 290 （ 52 ）： 30947 - 30961 .

CHEN X ， ASHRAF S ， ASHRAF N ， et al . UCP3 （uncoupling protein 3） insufficiency exacerbates left ventricular diastolic dysfunction during angiotensin Ⅱ-induced hypertension ［J］. J Am Heart Assoc ， 2021 ， 10 （ 18 ）： e022556 .

YANG K C ， TSENG Y T ， NERBONNE J M . Exercise training and PI3K α -induced electrical remodeling is independent of cellular hypertrophy and Akt signaling ［J］. J Mol Cell Cardiol ， 2012 ， 53 （ 4 ）： 532 - 541 .

MCLEAN B A ， PATEL V B ， ZHABYEYEV P ， et al . PI3K α pathway inhibition with doxorubicin treatment results in distinct biventricular atrophy and remodeling with right ventricular dysfunction ［J］. J Am Heart Assoc ， 2019 ， 8 （ 9 ）： e010961 .

YANG K C ， JAY P Y ， MCMULLEN J R ， et al . Enhanced cardiac PI3K α signalling mitigates arrhythmogenic electrical remodelling in pathological hypertrophy and heart failure ［J］. Cardiovasc Res ， 2022 ， 93 （ 2 ）： 252 - 262 .

CHEN H Y ， FANG Z ， LIN S L ， et al . L1CAM mimetic compound duloxetine improves cognitive impairment in 5×FAD mice and protects A β 1-42 -damaged HT22 cells ［J］. Eur J Pharmacol ， 2025 ， 997 ： 177476 .

WANG D Y ， HU B ， XU G T ， et al . L1 cell adhesion molecule may be a protective molecule for atrial fibrillation in patients with valvular heart disease ［J］. Heliyon ， 2023 ， 9 （ 6 ）： e16831 .

QI Q B ， MENZAGHI C ， SMITH S ， et al . Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels ［J］. Hum Mol Genet ， 2012 ， 21 （ 21 ）： 4774 - 4780 .

XU X ， LI H L ， WEI Q X ， et al . Novel targets in a high-altitude pulmonary hypertension rat model based on RNA-seq and proteomics ［J］. Front Med ， 2021 ， 8 ： 742436 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effect and Mechanism of Xiao Qinglongtang Against Right Ventricular Dysfunction in Rats with Pulmonary Arterial Hypertension Induced by Monocrotaline

Mechanism of Xiao Qinglongtang Intervening Ferroptosis in Allergic Rhinitis Rats via Regulating SIRT1/SLC7A11 Signaling Pathway

Proteomics-based Investigation of Therapeutic Effect and Mechanism of Verbenalin on Lung Injury in Mice Infected with Human Coronavirus-229E

Mechanism of Huangqi Gegen Decoction in Treatment of Type 2 Diabetes Mellitus via Intestinal Mucosal Barrier

Establishment and Evaluation of Mouse Model of Ischemic Heart Disease with Qi and Yin Deficiency Syndrome Based on Proteomics

Related Author

JI Yuanyuan

ZHU Hong

AN Jingjuan

XIN Heng

SUN Qiyue

GUO Shanshan

GAO Shuangrong

BAO Lei

Related Institution

The Second Affiliated Hospital of Nanjing University of Chinese Medicine

Nanjing First Hospital

Institute of Chinese Materia Medica，China Academy of Chinese Medical Sciences

Shanxi Key Laboratory of Innovative Drug for Treatment of Serious Diseases Basing on Chronic Inflammation，College of Traditional Chinese Medicine and Food Engineering， Shanxi University of Chinese Medicine

Beijing University of Chinese Medicine

AI问答

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰