發(fā)布時間：2022-11-05 05:48

　　平滑肌是機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,這是維持機體生理穩(wěn)態(tài)平衡的基本保障。平滑肌的收縮異�？蓪е乱幌盗屑膊�,如高血壓、血管痙攣、胃腸功能障礙、哮喘等。業(yè)已證實,平滑肌收縮主要由鈣信號和鈣敏機制調(diào)節(jié),其中當鈣敏機制異常時可導致平滑肌收縮行為異常,進而導致各種疾病的發(fā)生。因此,研究鈣敏機制不但對認識平滑肌的收縮規(guī)律有重要意義,而且對認識平滑肌相關(guān)疾病的發(fā)病機制亦具有重要意義。目前研究認為:MLCP活性調(diào)節(jié)是鈣敏機制的基礎(chǔ),其中鈣敏收縮是通過抑制MLCP的活性來實現(xiàn)的,主要可通過ROCK/MYPT1和PKC/CPI-17/PP1c兩個信號通路完成。我們曾發(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)鍵機制。遺憾的是,目前關(guān)于PKC/CPI-17/PP1c調(diào)節(jié)鈣敏收縮機制的證據(jù)均來自于體外細胞和藥理學觀察,在平滑肌鈣敏收縮的功能貢獻仍不知曉。為此,我們通過CRISPR/Cas9基因編輯技術(shù),分別在小鼠CPI-17基因位點敲除了 11... 

【文章頁數(shù)】：104 頁

【學位級別】：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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