平滑肌是機(jī)體空腔臟器的主要組織結(jié)構(gòu),其基本功能是通過收縮來產(chǎn)生一定的張力,這是維持機(jī)體生理穩(wěn)態(tài)平衡的基本保障。平滑肌的收縮異常可導(dǎo)致一系列疾病,如高血壓、血管痙攣、胃腸功能障礙、哮喘等。業(yè)已證實(shí),平滑肌收縮主要由鈣信號(hào)和鈣敏機(jī)制調(diào)節(jié),其中當(dāng)鈣敏機(jī)制異常時(shí)可導(dǎo)致平滑肌收縮行為異常,進(jìn)而導(dǎo)致各種疾病的發(fā)生。因此,研究鈣敏機(jī)制不但對(duì)認(rèn)識(shí)平滑肌的收縮規(guī)律有重要意義,而且對(duì)認(rèn)識(shí)平滑肌相關(guān)疾病的發(fā)病機(jī)制亦具有重要意義。目前研究認(rèn)為:MLCP活性調(diào)節(jié)是鈣敏機(jī)制的基礎(chǔ),其中鈣敏收縮是通過抑制MLCP的活性來實(shí)現(xiàn)的,主要可通過ROCK/MYPT1和PKC/CPI-17/PP1c兩個(gè)信號(hào)通路完成。我們?cè)l(fā)現(xiàn)MYPT1 T694的磷酸化是組成性的,與ROCK活性無關(guān)。由此提示ROCK/MYPT1途徑并不參與平滑肌的鈣敏調(diào)節(jié),PKC/CPI-17/PP1c途徑可能是鈣敏收縮的關(guān)鍵機(jī)制。遺憾的是,目前關(guān)于PKC/CPI-17/PP1c調(diào)節(jié)鈣敏收縮機(jī)制的證據(jù)均來自于體外細(xì)胞和藥理學(xué)觀察,在平滑肌鈣敏收縮的功能貢獻(xiàn)仍不知曉。為此,我們通過CRISPR/Cas9基因編輯技術(shù),分別在小鼠CPI-17基因位點(diǎn)敲除了 11... 

【文章頁數(shù)】：104 頁

【學(xué)位級(jí)別】：博士

【文章目錄】：
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
致謝



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