Effect of Xuefu Zhuyu Decoction on Pulmonary Vascular Remodeling in Hypoxic Pulmonary Hypertension Based on LncRNA MALAT1 Regulating SRSF1/mTORC1/4E-BP1 Signaling Axis
10.16466/j.issn1005-5509.2025.07.001
- VernacularTitle:基于lncRNA MALAT1调控SRSF1/mTORC1/4E-BP1信号轴研究血府逐瘀汤对HPH肺血管重构的作用
- Author:
Minjing LI
1
;
Ye CHEN
;
Weisi WANG
Author Information
1. 浙江中医药大学附属第二医院 杭州 310005
- Publication Type:Journal Article
- Keywords:
hypoxic pulmonary hypertension;
vascular remodeling;
PASMCs;
Xuefu Zhuyu Decoction;
lncRNA MALAT1;
SRSF1;
mTORC1;
4E-BP1
- From:
Journal of Zhejiang Chinese Medical University
2025;49(7):799-808
- CountryChina
- Language:Chinese
-
Abstract:
[Objective]To explore the effect of Xuefu Zhuyu Decoction on pulmonary vascular remodeling in hypoxic pulmonary hypertension(HPH)through regulating long non-coding RNA metastasis-related lung adenocarcinoma transcript 1(lncRNA MALAT1),and further verify the specific molecular mechanism.[Methods]The HPH model of rat was established by using a low-pressure hypoxia method,and intragastric administration of Xuefu Zhuyu Decoction was performed at doses of 4.5 g/(kg·d)and 8.75 g/(kg·d).The model construction was evaluated by rat right ventricular systolic pressure and Fulton index,and then the pulmonary artery vascular remodeling was observed by hematoxylin-eosin(HE)staining and immunohistochemistry.The drug-containing serum of rats was prepared,and pulmonary artery smooth muscle cells(PASMCs)of rat were extracted.The cell model was then established under hypoxic conditions.PASMCs activity and migration capacity were detected by cell counting kit-8(CCK-8)and Transwell respectively.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression of lncRNA MALAT1 and serine/arginine-rich splicing factor 1(SRSF1).Western blot was employed to analyze the expression of related proteins in cells and tissues.[Results]Compared with model group,the right ventricular systolic blood pressure and ventricular hypertrophy in Xuefu Zhuyu Decoction group were significantly relieved(P＜0.05),and the remodeling of pulmonary artery was alleviated.lncRNA MALAT1 was significantly overexpressed in the pulmonary artery tissues of rats in model group,and the downstream SRSF1/mammalian target of rapamycin complex 1(mTORC1)/eukaryotic translation initiation factor 4E-binding protein 1(4E-BP1)signaling axis was significantly activated.Compared with model group,the expressions of lncRNA MALAT1 and SRSF1/mTORC1/4E-BP1 signaling axis-related proteins in the pulmonary artery tissues of rats in Xuefu Zhuyu Decoction administrated group were significantly decreased(P＜0.05).In vitro,PASMCs treated with drug-containing serum of Xuefu Zhuyu Decoction exhibited significantly reduced proliferation(P＜0.05)and migration abilities,decreasing expression of lncRNA MALAT1(P＜0.05).Meanwhile,the expression of SRSF1/mTORC1/4E-BP1 signaling axis-related proteins was significantly decreased(P＜0.05).Furthermore,through the transfection with overexpression plasmids of lncRNA MALAT1 or SRSF1,the expression of lncRNA MALAT1 was increased(P＜0.05),the cell proliferation(P＜0.05)and migration abilities were recovered,and the expression of SRSF1/mTORC1/4E-BP1 signal axis-related proteins was increased(P＜0.05),indicating that the above inhibitory effects were significantly reversed.[Conclusion]Xuefu Zhuyu Decoction can alleviate HPH vascular remodeling by down-regulating lncRNA MALAT1 expression,and regulating SRSF1/mTORC1/4E-BP1 signaling axis.
