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  

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

作　　者：贺红艳 晁满香 翟翠 张晴 李海燕 HE Hongyan;CHAO Manxiang;ZHAI Cui;ZHANG Qing;LI Haiyan(Department of Medical Technology,Xi’an Medical University,Xi’an 710021,China;Shaanxi Key Laboratory of Brain Disorders/Institute of Basic and Translational Medicine,Xi’an Medical University,Xi’an 710021,China;Department of Neurology,Air Force 986th Hospital,Air Force Military Medical University,Xi’an 710000,China)

机构地区：[1]西安医学院医学技术学院,西安710021 [2]西安医学院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 [3]空军军医大学空军第九八六医院神经内科,西安710000

出　　处：《现代检验医学杂志》2024年第4期45-49,共5页Journal of Modern Laboratory Medicine

基　　金：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)。

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。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.

关 键 词：肺动脉高压 血管重塑 Twist相关蛋白1 

分 类 号：R-332[医药卫生]