研究背景:糖尿病胃輕癱（Diabetic gastroparesis,DGP）是糖尿病胃腸道最常見的并發(fā)癥,常表現(xiàn)為非機(jī)械性梗阻情況下的胃動(dòng)力障礙及胃排空延遲,目前DGP發(fā)病機(jī)制尚不明確。截止目前,自主神經(jīng)病變、急性血糖升高及間質(zhì)卡哈爾細(xì)胞（Interstitial Cahal cell,ICC）的損傷和缺失被認(rèn)為是影響胃動(dòng)力的主要因素。胰島素樣生長因子-1（Insulin-like growth factor-1,IGF-1）主要由肝臟分泌,是結(jié)構(gòu)與胰島素有一定相似性的蛋白多肽。近年來的眾多研究發(fā)現(xiàn),IGF-1與糖尿病慢性并發(fā)癥的發(fā)生、發(fā)展有著密切的關(guān)系。磷脂酰肌醇3激酶（Phosphoinositide3-kinase,PI3K）-絲氨酸蛋白激酶（Akt）通路是細(xì)胞內(nèi)重要的信號通路。PI3K-Akt通路在許多糖尿病并發(fā)癥中被激活,且為IGF-1下游信號。Zhang等人研究發(fā)現(xiàn),PI3K-Akt通路參與了 DGP發(fā)生,并且隨胃輕癱的發(fā)展其表達(dá)逐漸降低。蛋白激酶C（Protein kinase C,PKC）家族有3種,包括經(jīng)典型、新型及非典型PKC,其中經(jīng)典型分為PKCα、PKCβⅠ、... 

【文章來源】：延邊大學(xué)吉林省 211工程院校

【文章頁數(shù)】：92 頁

【學(xué)位級別】：博士

【文章目錄】：
摘要
ABSTRACT
ABBEVIATIONS
1. INTRODUCTION
    1.1 The pathogenesis of DGP
        1.1.1 Interstitial cells of Cajal （ICC）
        1.1.2 Extrinsic nervous system
        1.1.3 Enteric nervous system lesion
        1.1.4 Gastric smooth muscle cells
        1.1.5 Immune Cells
        1.1.6 Macrophages
        1.1.7 Hyperglycemia
    1.2 Insulin-like growth factor-1 and diabetes
    1.3 Endoplasmic reticulum stress and autophagy
    1.4 Study design
2. MATERIALS AND METHODS
    2.1 Materials
    2.2 Methods
        2.2.1 Diabetic rat model establishment and grouping
        2.2.2 Immunofluorescence staining of tissue sections
        2.2.3 Western blot analysis of GRP78,CHOP, LC3Ⅱ, PI3K, p-Akt, PKCα, PKCβ1 proteinexpression in rat gastric smooth muscle tissues
        2.2.4 Primary culture of rat gastric smooth muscle cells and grouping
        2.2.5 Detection of PKC activity in rat gastric smooth muscle cells by ELISA method
2+ concentration in rat gastric smoothmuscle cells by confocal laser-scanning microscopy">        2.2.6 Detection of canges in intracellular Ca²⁺ concentration in rat gastric smoothmuscle cells by confocal laser-scanning microscopy
        2.2.7 Detection of GRP78 and LC3 in rat gastric smooth muscle cells by confocallaser-scanning microscopy
        2.2.8 Western blot analysis of GRP78,CHOP, LC3Ⅱ,PI3K, p-Akt, PKCα, PKCβ1,p-PKCα, p-PKCβ1 protein expression in gastric smooth muscle cells
        2.2.9 Statistical analysis
3. RESULTS
    3.1 Results of immunofluorescence staining of GRP78 and LC3 in rat gastric smoothmuscle tissues
    3.2 Western blot assay results of GRP78,CHOP, LC3Ⅱ,PI3K, p-Akt, PKCα,PKCβ1protein expression in rat gastric smooth muscle tissues of each group
    3.3 Identification of gastric smooth muscle cell
    3.4 PKC activity in rat gastric smooth muscle cells as detected by ELISA method
2+ concentration in rat gastric smooth muscle cells as detected byconfocal laser-scanning microscopy">    3.5 Changes in Ca²⁺ concentration in rat gastric smooth muscle cells as detected byconfocal laser-scanning microscopy
    3.6 GRP78, LC3 expression in rat gastric smooth muscle cells as detected by confocallaser-scanning microscopy
    3.7 Expression of GRP78, CHOP, LC3Ⅱ,PI3K,p-Akt, PKCα, PKCβ1,p-PKCα, p-PKCβ1protein expression in vitro-cultured rat gastric smooth muscle cells as detected by westernblot assay
4. DISCUSSION
5. CONCLUSIONS
REFERENCES
致謝
攻讀博士期間發(fā)表的論文


【參考文獻(xiàn)】：
期刊論文
[1]Sequential blood purification therapy for critical patients with hyperlipidemic severe acute pancreatitis[J]. Hong-Liang Wang,Kai-Jiang Yu.  World Journal of Gastroenterology. 2015(20)
[2]C-type natriuretic-peptide-potentiated relaxation response of gastric smooth muscle in streptozotocin-induced diabetic rats[J]. Ying-Lan Cai, Dong-Yuan Xu, Xiang-Lan Li, Zheng Jin, Department of Physiology, Yanbian University School of Medicine, Yanji 133000, Jilin Province, China Zhang-Xun Qiu, Wen-Xie Xu, Department of Physiology, Shanghai Jiaotong University School of Medicine, Shanghai 200240, China.  World Journal of Gastroenterology. 2009(17)



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