生物活性肽Vglycin治療2型糖尿病和非酒精性脂肪肝病作用機(jī)理
發(fā)布時間：2021-07-03 00:09
2型糖尿病（T2D）和非酒精性脂肪肝�。∟AFLD）均屬于全球廣泛流行的代謝綜合征,肥胖是誘發(fā)兩種疾病的最主要因素,胰島素抵抗則是二者的致病機(jī)制之一。導(dǎo)致肥胖的原因有很多,從代謝組學(xué)的角度來看,最主要的原因是能量過剩的飲食習(xí)慣和缺乏運(yùn)動的生活方式。肥胖一方面會引發(fā)多種器官和組織的胰島素抵抗,另一方面產(chǎn)生的多種炎性因子又能進(jìn)一步加劇胰島素抵抗的程度。2型糖尿病的臨床典型癥狀就是持續(xù)的高血糖和胰島素抵抗,二者的共同作用會造成糖耐量受損。非酒精性脂肪肝病除了表現(xiàn)出胰島素抵抗這一病理特征外,還有肝功能異常、肝臟脂肪變性和肝細(xì)胞甘油三酯增多等現(xiàn)象�？刂坪没颊叩难撬绞侵委�2型糖尿病的關(guān)鍵,同時也是預(yù)防或延緩糖尿病并發(fā)癥發(fā)生的關(guān)鍵。醫(yī)學(xué)和生物學(xué)工作者一直致力于尋找到更加安全有效的藥物來治療2型糖尿病和非酒精性脂肪肝病。生物活性肽Vglycin是本實(shí)驗室研究人員從萌發(fā)的豌豆種子和大豆種子中分離出的一個含有37個氨基酸的多肽。前期研究中發(fā)現(xiàn)Vglycin可以使2型糖尿病Wistar受損空腹血糖得到恢復(fù)�；趯glycin的初步研究,我們認(rèn)為Vglycin在治療2型糖尿病以及非酒精性脂肪肝病上會有很...
【文章來源】：華中科技大學(xué)湖北省 211工程院校 985工程院校 教育部直屬院校
【文章頁數(shù)】：119 頁
【學(xué)位級別】：博士
【部分圖文】：
基因和環(huán)境在2型糖尿病發(fā)生中的作用[19]Figure1-2.Roleofgenesandtheenvironmentinthedevelopmentofobesityandtype2diabetes.
圖1-4非酒精性脂肪肝疾病病理生理學(xué)[130]Fig. 1-4. Pathophysiology ofNAFLD/NASHObesity and metabolic syndrome lead to adipose tissue (AT) dysfunction causing the release of excessFFAs from the adipocytes into the portal circulation, which leads to accumulation of excess TGs in thehepatocytes. In addition to FFAs,the adipocytes release increased levels of inflammatory mediators,MCP-1 and IL-6, anddecreased levels of adiponectin. Furthermore, the gut releases bacterial products,such asLPS and other PAMPs and DAMPS, which enter the liver and activate pattern recognitionreceptors, such as the TLR4 and NLRP3 inflammasome, among others, on KCs (and otherimmunecells), hepatocytes, and HSCs, to produce inflammatory mediators like ROS, IL-1 b, TNF-a,Inos,and IL-6, which, in turn, promote hepatocyte injury and IR and inflammation in thehepaticimmune cells and activate fibrogenesis in the stellate cells, thereby accelerating NASHprogression. In addition, hepatic iron overload leads to oxidative stress and NF-kB–mediatedinflammation, promoting NAFLD progression. iNOS, inducible nitric oxide synthase; TGF,transforming growth factor.1.6 非酒精性脂肪肝疾病的治療
的 Vglycin 生理鹽水溶液進(jìn)行口腔灌胃給藥，直至動物實(shí)驗結(jié)束，實(shí)驗流程如圖 2-3所示。圖2-3 2型糖尿病小鼠模型構(gòu)建Figure 2-3 T2D mouse experimental model strategy2.3.2 空腹血糖和隨機(jī)血糖檢測在高脂飼料喂養(yǎng) 3 個月后完成各組小鼠相應(yīng)的造模處理，每日對治療組小鼠（HFD+Vglycin 組和 HFD+STZ+Vglycin 組）進(jìn)行 Vglycin 給藥治療，開始給藥治療1 周后每周檢測一次各組小鼠空腹血糖或隨機(jī)血糖，采血時用手術(shù)刀片在鼠尾最末端切割一條小口，擠出受試所需血量即可，用碘伏消毒后放回鼠籠，注意觀察防止感染或者斷尾現(xiàn)象的發(fā)生。2.3.3 葡萄糖耐受試驗（GTT）口服葡萄糖耐受試驗（Oral glucose tolerance test，OGTT）和腹腔注射葡萄糖耐受實(shí)驗（Intraperitoneal glucose tolerance test，IPGTT）分別在實(shí)驗前將小鼠禁食過夜（16h），以 1.5g/kg body weight 的葡萄糖溶液進(jìn)行灌胃或腹腔注射處理
【參考文獻(xiàn)】：
期刊論文
[1]Fructose as a key player in the development of fatty liver disease[J]. Metin Basaranoglu,Gokcen Basaranoglu,Tevfik Sabuncu,Hakan Sentürk. World Journal of Gastroenterology. 2013(08)
本文編號：3261452
【文章來源】：華中科技大學(xué)湖北省 211工程院校 985工程院校 教育部直屬院校
【文章頁數(shù)】：119 頁
【學(xué)位級別】：博士
【部分圖文】：
基因和環(huán)境在2型糖尿病發(fā)生中的作用[19]Figure1-2.Roleofgenesandtheenvironmentinthedevelopmentofobesityandtype2diabetes.
圖1-4非酒精性脂肪肝疾病病理生理學(xué)[130]Fig. 1-4. Pathophysiology ofNAFLD/NASHObesity and metabolic syndrome lead to adipose tissue (AT) dysfunction causing the release of excessFFAs from the adipocytes into the portal circulation, which leads to accumulation of excess TGs in thehepatocytes. In addition to FFAs,the adipocytes release increased levels of inflammatory mediators,MCP-1 and IL-6, anddecreased levels of adiponectin. Furthermore, the gut releases bacterial products,such asLPS and other PAMPs and DAMPS, which enter the liver and activate pattern recognitionreceptors, such as the TLR4 and NLRP3 inflammasome, among others, on KCs (and otherimmunecells), hepatocytes, and HSCs, to produce inflammatory mediators like ROS, IL-1 b, TNF-a,Inos,and IL-6, which, in turn, promote hepatocyte injury and IR and inflammation in thehepaticimmune cells and activate fibrogenesis in the stellate cells, thereby accelerating NASHprogression. In addition, hepatic iron overload leads to oxidative stress and NF-kB–mediatedinflammation, promoting NAFLD progression. iNOS, inducible nitric oxide synthase; TGF,transforming growth factor.1.6 非酒精性脂肪肝疾病的治療
的 Vglycin 生理鹽水溶液進(jìn)行口腔灌胃給藥，直至動物實(shí)驗結(jié)束，實(shí)驗流程如圖 2-3所示。圖2-3 2型糖尿病小鼠模型構(gòu)建Figure 2-3 T2D mouse experimental model strategy2.3.2 空腹血糖和隨機(jī)血糖檢測在高脂飼料喂養(yǎng) 3 個月后完成各組小鼠相應(yīng)的造模處理，每日對治療組小鼠（HFD+Vglycin 組和 HFD+STZ+Vglycin 組）進(jìn)行 Vglycin 給藥治療，開始給藥治療1 周后每周檢測一次各組小鼠空腹血糖或隨機(jī)血糖，采血時用手術(shù)刀片在鼠尾最末端切割一條小口，擠出受試所需血量即可，用碘伏消毒后放回鼠籠，注意觀察防止感染或者斷尾現(xiàn)象的發(fā)生。2.3.3 葡萄糖耐受試驗（GTT）口服葡萄糖耐受試驗（Oral glucose tolerance test，OGTT）和腹腔注射葡萄糖耐受實(shí)驗（Intraperitoneal glucose tolerance test，IPGTT）分別在實(shí)驗前將小鼠禁食過夜（16h），以 1.5g/kg body weight 的葡萄糖溶液進(jìn)行灌胃或腹腔注射處理
【參考文獻(xiàn)】：
期刊論文
[1]Fructose as a key player in the development of fatty liver disease[J]. Metin Basaranoglu,Gokcen Basaranoglu,Tevfik Sabuncu,Hakan Sentürk. World Journal of Gastroenterology. 2013(08)
本文編號：3261452
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