下丘脑室旁核CBS通过影响PGC-1α降低自发性高血压大鼠的血压  

The hypothalamic paraventricular nucleus CBS reduces blood pressure in spontaneously hypertensive rats by affecting PGC-1α

作　　者：于晓静 高雅楠 李迎 涂丽梅 高千喜 孙要军[3] 和荣丽[3] 康玉明 史小莲 YU Xiaojing;GAO Yanan;LI Ying;TU Limei;GAO Qianxi;SUN Yaojun;HE Rongli;KANG Yuming;SHI Xiaolian(Department of Physiology and Pathophysiology,School of Basic Medical Sciences,Xi’an Jiaotong University Health Science Center,Xi’an 710061;School of Industry,Shanxi Medical University,Taiyuan 030001;School of Basic Medical Sciences,Shanxi Medical University,Taiyuan 030001;Department of Pharmacology,School of Basic Medical Sciences,Xi’an Jiaotong University Health Science Center,Xi’an 710061,China)

机构地区：[1]西安交通大学医学部基础医学院生理学与病理生理学系,陕西西安710061 [2]山西医科大学产业学院,山西太原030001 [3]山西医科大学基础医学院生物制药教研室,山西太原030001 [4]西安交通大学医学部基础医学院药理学系,陕西西安710061

出　　处：《西安交通大学学报(医学版)》2025年第2期227-237,共11页Journal of Xi’an Jiaotong University(Medical Sciences)

基　　金：国家自然科学基金资助项目(No.82070440,No.82070439);陕西省重点研发计划一般项目(No.2023-YBSF-153);陕西省自然科学基础研究计划资助项目(No.2024JC-YBMS-764)。

摘　　要：目的 阐明胱硫醚-β-合酶(CBS)过表达对过氧化物酶体增殖物激活受体γ辅激活因子-1α(PGC-1α)转录的影响及发挥降压作用的具体机制。方法 向自发性高血压大鼠(SHR)的下丘脑室旁核(PVN)单用/同时注射过表达CBS和敲减PGC-1α的腺相关病毒(AAV),监测大鼠血压,ELISA检测血浆去甲肾上腺素(NE)水平,RT-qPCR和免疫荧光染色检测PVN炎症反应、氧化应激水平及酪氨酸羟化酶(TH)的表达。结果 PVN过表达CBS可以增加SHR的PVN中CBS(约3.8倍,P<0.05)及PGC-1α(约1.6倍,P<0.05)的转录水平;PVN过表达CBS可以降低SHR的血压(从177.81 mmHg降至128.77 mmHg,P<0.001),但PVN敲减PGC-1α会减弱过表达CBS降低SHR血压的作用(从128.77 mmHg升至152.79 mmHg,P<0.05);PVN过表达CBS可以缓解PVN炎症反应、氧化应激,但同时过表达CBS和敲减PGC-1α时这种作用被减弱甚至消除。结论 PVN过表达CBS可以降低SHR的血压,并且这种效应可能是通过增加PGC-1α的转录水平,缓解PVN炎症反应、氧化应激,改善交感神经兴奋而实现。Objective To elucidate how the overexpression of cystathionine-β-synthase(CBS)plays an antihypertensive role by affecting peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α)expression.Methods The adeno-associated viruses(AAVs),ones that overexpressed CBS,and another knocked down PGC-1α,were injected into the hypothalamic paraventricular nucleus(PVN)of spontaneously hypertensive rats(SHRs).The rats’blood pressure was monitored,and the level of norepinephrine(NE)was examined by ELISA;PVN inflammatory response,oxidative stress and tyrosine hydroxylase(TH)expression were detected with RT-qPCR and immunofluorescence.Results PVN overexpression of CBS could increase the transcription level of CBS(by 3.8 times,P<0.05)and PGC-1α(by 1.6 times,P<0.05)in PVN of SHR.PVN overexpression of CBS could reduce blood pressure in SHR(from 177.81 mmHg to 128.77 mmHg,P<0.001),but PVN knockdown of PGC-1αweakened such effect(from 128.77 mmHg to 152.79 mmHg,P<0.05).PVN overexpression of CBS could alleviate PVN inflammatory response and oxidative stress,but this effect was weakened or even eliminated when knocking down PGC-1αwas performed at the same time.Conclusion PVN overexpression of CBS can reduce blood pressure in SHR,and this effect may be achieved by increasing the transcriptional level of PGC-1α,alleviating PVN inflammatory response,oxidative stress,and improving sympathetic nerve excitation.

关 键 词：高血压 下丘脑室旁核(PVN) 胱硫醚-β-合酶(CBS) 过氧化物酶体增殖物激活受体γ辅激活因子-1α(PGC-1α) 氧化应激 

分 类 号：R544.1[医药卫生—心血管疾病]