肥胖相关高血压的形成需要CPI-17调节的血管平滑肌钙增敏机制

发布时间：2022-11-05 05:48

　　平滑肌是机体空腔脏器的主要组织结构,其基本功能是通过收缩来产生一定的张力,这是维持机体生理稳态平衡的基本保障。平滑肌的收缩异常可导致一系列疾病,如高血压、血管痉挛、胃肠功能障碍、哮喘等。业已证实,平滑肌收缩主要由钙信号和钙敏机制调节,其中当钙敏机制异常时可导致平滑肌收缩行为异常,进而导致各种疾病的发生。因此,研究钙敏机制不但对认识平滑肌的收缩规律有重要意义,而且对认识平滑肌相关疾病的发病机制亦具有重要意义。目前研究认为:MLCP活性调节是钙敏机制的基础,其中钙敏收缩是通过抑制MLCP的活性来实现的,主要可通过ROCK/MYPT1和PKC/CPI-17/PP1c两个信号通路完成。我们曾发现MYPT1 T694的磷酸化是组成性的,与ROCK活性无关。由此提示ROCK/MYPT1途径并不参与平滑肌的钙敏调节,PKC/CPI-17/PP1c途径可能是钙敏收缩的关键机制。遗憾的是,目前关于PKC/CPI-17/PP1c调节钙敏收缩机制的证据均来自于体外细胞和药理学观察,在平滑肌钙敏收缩的功能贡献仍不知晓。为此,我们通过CRISPR/Cas9基因编辑技术,分别在小鼠CPI-17基因位点敲除了 11... 

【文章页数】：104 页

【学位级别】：博士

【文章目录】：
摘要
Abstract
Abbreviations/Acronyms
Chapter I A Brief Review: Vascular Smooth Muscle Contractionand Obesity Related Hypertension
    1. Vascular smooth muscle contraction
        1.1 Vascular smooth muscle
        1.2 MLCK and RLC phosphorylationin vascular smooth muscle contraction
        1.3 Calcium sensitivity
        1.4 MYPT1
    2. PKC/CPI-17 in vascular smooth muscle contractionand blood pressure regulation
        2.1 Structure and function of CPI-17 in vascular smooth muscle
        2.2 CPI-17 in diseases
    3. Blood pressure regulation and hypertension
        3.1 Blood pressure regulation
        3.2 Renal-body fluid feedback and RASin blood pressure control and hypertension
        3.3 Vascular smooth muscle contractiondirectly regulate blood pressure
    4. Obesity related hypertension
        4.1 The epidemic of obesity
        4.2 Closely relationship between obesity and hypertension
        4.3 Animal models of obesity related hypertension
        4.4 sympathetic nervous system overactivityin obesity related hypertension
        4.5 Renal dysfunction in obesity related hypertension
        4.6 Renin-angiotensin system in obesity related hypertension
        4.7 Hyperaldosteronemia in obesity related hypertension
    References
Chapter Ⅱ CPI-17 Regulated Calcium Sensitization ofVascular Smooth Muscles Is Required for Obesity Related Hypertension
    Introduction
    Materials and methods
    Results
    Discussion
    References
Publications
致谢



本文编号：3702026