[1]贺红艳a,晁满香,翟 翠b,等.TWIST1 通过激活自噬促进肺动脉高压大鼠模型肺血管重塑作用及机制的实验研究[J].现代检验医学杂志,2024,39(04):45-49.[doi:10.3969/j.issn.1671-7414.2024.04.009]
　HE Hongyana,CHAO Manxiang,ZHAI Cuib,et al.Experimental Study on the Effect and Mechanism of TWIST1 Promoting Pulmonary Vascular Remodeling in a Rat Model of Pulmonary Arterial Hypertension by Activation of Autophagy[J].Journal of Modern Laboratory Medicine,2024,39(04):45-49.[doi:10.3969/j.issn.1671-7414.2024.04.009]
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TWIST1 通过激活自噬促进肺动脉高压大鼠模型肺血管重塑作用及机制的实验研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年04期
页码:
45-49
栏目:
论著
出版日期:
2024-07-15

文章信息/Info

Title:
Experimental Study on the Effect and Mechanism of TWIST1 Promoting Pulmonary Vascular Remodeling in a Rat Model of Pulmonary Arterial Hypertension by Activation of Autophagy
文章编号:
1671-7414（2024）04-045-05
作者:
贺红艳1a; 晁满香2; 翟 翠1b; 张 晴1a; 李海燕1a
（1. 西安医学院 a. 医学技术学院；b. 基础与转化医学研究所/ 陕西省脑疾病防治重点实验室，西安710021；2. 空军军医大学空军第九八六医院神经内科，西安 710000）
Author(s):
HE Hongyan1a;  CHAO Manxiang2;  ZHAI Cui1b;  ZHANG Qing1a;  LI Haiyan1a
（1a. Department of Medical Technology; 1b. Shaanxi Key Laboratory of Brain Disorders/Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an 710021, China; 2. Department of Neurology, Air Force 986th Hospital, Air Force Military Medical University, Xi’an 710000, China）
关键词:
肺动脉高压; 血管重塑; Twist 相关蛋白1
分类号:
R-332
DOI:
10.3969/j.issn.1671-7414.2024.04.009
文献标志码:
A
摘要:
目的 探讨Twist 相关蛋白1（Twist-related protein 1，TWIST1）对野百合碱（Monocrotaline，MCT）诱导的肺动脉高压（pulmonary arterial hypertension，PAH）大鼠肺血管重塑的影响及机制。方法 将50 只健康雄性SD 大鼠，随机分为5 组，即对照组、模型组、二甲基亚砜（Dimethyl sulfoxide，DMSO）溶剂处理的模型组、TWIST1 抑制剂Harmine组、自噬抑制剂羟氯喹组。检测右心室收缩压（RVSP），右心室肥厚指数（RVHI）和内膜厚度百分比（MT%）以评估大鼠PAH 的发展。采用免疫印迹法检测TWIST1，自噬相关蛋白LC3B 以及RND3 的蛋白质水平。结果 与对照组比较，MCT 诱导的PAH 大鼠中TWIST1 和LC3B 表达增加，分别为对照组的2.32±0.22 倍和0.87±0.19 倍，差异具有统计学意义（t=15.812，11.227，均P<0.001）；同时RND3 表达下调，为对照组的0.32±0.07 倍，差异具有统计学意义（t=-13.003，P<0.001）。给与TWIST1 抑制剂Harmine 或自噬抑制剂羟氯喹可显著抑制MCT 诱导的自噬激活和RND3 表达下调，同时降低了MCT 诱导的PAH 大鼠的RVSP，RVHI 和MT%，差异具有统计学意义（t=-24.277~16.636，均P<0.001）。结论 TWIST1 通过诱导自噬激活促进肺血管重塑，促进PAH 的发生发展。
Abstract:
Objective To investigate the effect and mechanism of Twist-related protein 1 (TWIST1) on pulmonary vascular remodeling induced by monocrotaline (MCT) in pulmonary arterial hypertension (PAH) rats. Methods A total of 50 healthy male Sprague Dawley (SD) rats were randomly divided into five groups including control group, MCT-treated group, MCT and dimethyl sulfoxide (DMSO)-treated group, MCT and harmine-treated group MCT and hydroxychloroquine (HCQ)-treated group. The right ventricle systolic pressure (RVSP) was measured, right ventricular hypertrophy index (RVHI) and percentage of medial wall thickness (MT%) to assess the development of PAH. The protein levels of TWIST1, autophagy markers LC3B and RND3 were determined using western blot. Results Compared with control group, expressions of TWIST1 and LC3B were increased by 2.32±0.22 folds and 0.87±0.19 folds in MCT-induced PAH group, with significant differences (t=15.812, 11.227, all P<0.001), while the protein level of RND3 in MCT-induced PAH rats was decreased by 0.32±0.07 folds compared with control group, with significant difference (t=-13.003, P<0.001). Administration of TWIST1 inhibitor Harmine or autophagy inhibitor hydroxychloroquine significantly suppressed MCT-induced increase in LC3B and down-regulation of RND3 expression, and reduced RVSP, RVHI and MT% expressions in MCT-induced PAH rats, with significant differences (t= -24.277~16.636, all P<0.001). Conclusion TWIST1 promotes pulmonary vascular remodeling by inducing autophagy activation, thus promoting the occurrence and development of PAH.

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备注/Memo

备注/Memo:
基金项目： 国家自然科学基金（81700546），陕西省科技厅自然科学基础研究计划项目（2023-JC-QN-0863），2023~2024 年度西安医学院校级科研项目（2023QN02），西安医学院第五批校级重点学科（医学技术12202306）。
作者简介： 贺红艳（1976-），女，硕士，讲师，研究方向：临床检验，E-mail：hehongyan@xiyi.edu.cn。
晁满香（1976-）女，学士，主治医师，Email：chaomanxiang@126.com，并列第一作者。
更新日期/Last Update: 2024-07-15