猕猴NAFLD组织病理学诊断及YAP介导的该病发病机制研究
发布时间：2021-08-18 20:33
近年来非酒精性脂肪肝病（NAFLD）对人类健康的危害不断增加,是当代医学领域的研究热点和挑战。本研究旨在探讨YAP（Yes associated protein）与TGF-β（Transforming growth factor-β）/Smad信号通路及其相互作用对NAFLD发生发展的调控机制,对NAFLD治疗靶点的发现具有重要的作用。猕猴高脂饲料饲喂两年,肝活检取材两条组织,分别4%多聚甲醛固定和液氮冰冻,采血做血液生化检测。HE、Masson、油红O染色筛查简单脂肪变性、NASH（Non-alcoholic steatohepatitis）、肝纤维化猕猴;免疫组织化学、实时荧光定量PCR分别检测目的蛋白表达位置及表达水平和mRNA相对表达量;大鼠肝细胞培养（5%CO2,10%FBS培养基）,MTT法做Verteporfin对细胞的毒性试验;实时荧光定量PCR检测细胞各目的基因的相对表达量;蛋白质印迹检测细胞目的蛋白质表达量。1.猕猴肝活检病理结果显示:猕猴肝脏正常的有23只,参考Elizabeth M.Brunt（1999,2005）评分标准,NASH评分1<...
【文章来源】：四川农业大学四川省 211工程院校
【文章页数】：63 页
【学位级别】：硕士
【部分图文】：
猕猴肝脏组织病理学变化HE20×,40×→：脂肪变性；：炎性细胞浸润Fig.1HistopathologicalchangesoflivertissueinmonkeysHE20×,40×→：Steatosis；：Inflammatorycellinfiltration
3.1.2 猕猴肝脏纤维增生检测NASH 及肝纤维化严重程度与肝脏相关疾病的发病率和死亡率密切相关[113]。实验 Masson 三色染色结果显示(见图 2)：在简单脂肪变性组中，16 只猕猴有轻肝纤维增生(1 期)，没有纤维化(2-3 期)的猕猴。在 NASH 组中，3 只猕猴纤维化期在(1 期)，5 只猕猴纤维化（2-3 期）。
图 3 猕猴肝脂滴沉积油红 O 染色 10×, 40×Fig. 3 Lipid droplet deposition in liver of monkey. Oil red O staining 10×, 40×(A) 图片显示油红 O 染色猕猴肝脏组织脂滴沉积；(B)脂滴积分光密度值统计。→：脂滴(A) Representative images of the oil red O staining show the accumulation lipid in the liver of differenthistological characteristics of monkeys. (B) Quantification shows the lipid integral optical density.→：Lipid droplets3.1.4 血液生化结果猕猴筛选结束后，统计每组血液生化结果(见表 4)。与正常和患有简单脂肪肝的猕猴相比，患有 NASH 的猕猴的 FPG 和 TG 显著升高（P <0.01），但是 ALB，HDL及 LDL 均在正常范围内。表 4 猕猴血液生化结果Table 4. Biochemical of the Study MonkeysVariables Normal (n =23) Simple steatosis (n = 45) NASH (n = 9)FPG(mmol/L) 4.77±0.54 4.69±0.477 6.27±1.65**LDL(mmol/L) 1.15±0.26 1.33±0.34 1.83±0.82
【参考文献】：
期刊论文
[1]Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy[J]. Maria Nicoline Baandrup Kristiansen,Sanne Skovg?rd Veidal,Kristoffer Tobias Gustav Rigbolt,Kirstine Sloth T?lb?l,Jonathan David Roth,Jacob Jelsing,Niels Vrang,Michael Feigh. World Journal of Hepatology. 2016(16)
[2]Insulin resistance in development and progression of nonalcoholic fatty liver disease[J]. Shahinul Alam,Golam Mustafa,Mahabubul Alam,Nooruddin Ahmad. World Journal of Gastrointestinal Pathophysiology. 2016(02)
[3]肠道菌群对非酒精性脂肪性肝病病变程度的影响[J]. 郑啼婴,李瑜元,聂玉强,曹杰,古维立,杜艳蕾,邱睿睿,周永健. 广州医科大学学报. 2016(01)
[4]Mechanism of action of gypenosides on type 2 diabetes and non-alcoholic fatty liver disease in rats[J]. Qin He,Jin-Ke Li,Fang Li,Ru-Gui Li,Guo-Qing Zhan,Gang Li,Wei-Xing Du,Hua-Bing Tan. World Journal of Gastroenterology. 2015(07)
[5]Non-alcoholic fatty liver disease: What the clinician needs to know[J]. Mariana Verdelho Machado,Helena Cortez-Pinto. World Journal of Gastroenterology. 2014(36)
[6]2型糖尿病合并非酒精性脂肪肝与糖尿病慢性并发症的相关性[J]. 赵新,陈延延,李晓通,耿静,肖金凤,朱铁虹. 中国慢性病预防与控制. 2014(01)
[7]非酒精性脂肪性肝病研究的关切点[J]. 曾民德. 肝脏. 2009(04)
[8]Metabolic syndrome and non-alcoholic fatty liver disease:Asian definitions and Asian studies[J]. Jian-Gao Fan and Yong-De Peng Center for Fatty Liver Disease & Department of Endocrinology, Shanghai First People’s Hospital, Jiaotong University, Shanghai 200080, China. Hepatobiliary & Pancreatic Diseases International. 2007(06)
[9]非酒精性脂肪性肝炎肝组织TNF-α、TGF-β1和Leptin的表达及意义[J]. 丁效蕙,赵景民,孙艳玲,周光德,潘登,杨建法,赵雨来. 解放军医学杂志. 2006(08)
[10]非酒精性脂肪性肝病诊疗指南[J]. Fatty Liver and Alcoholic Liver Disease Study Group of the Chinese Liver Disease Association.. 中华肝脏病杂志. 2006(03)
本文编号：3350580
【文章来源】：四川农业大学四川省 211工程院校
【文章页数】：63 页
【学位级别】：硕士
【部分图文】：
猕猴肝脏组织病理学变化HE20×,40×→：脂肪变性；：炎性细胞浸润Fig.1HistopathologicalchangesoflivertissueinmonkeysHE20×,40×→：Steatosis；：Inflammatorycellinfiltration
3.1.2 猕猴肝脏纤维增生检测NASH 及肝纤维化严重程度与肝脏相关疾病的发病率和死亡率密切相关[113]。实验 Masson 三色染色结果显示(见图 2)：在简单脂肪变性组中，16 只猕猴有轻肝纤维增生(1 期)，没有纤维化(2-3 期)的猕猴。在 NASH 组中，3 只猕猴纤维化期在(1 期)，5 只猕猴纤维化（2-3 期）。
图 3 猕猴肝脂滴沉积油红 O 染色 10×, 40×Fig. 3 Lipid droplet deposition in liver of monkey. Oil red O staining 10×, 40×(A) 图片显示油红 O 染色猕猴肝脏组织脂滴沉积；(B)脂滴积分光密度值统计。→：脂滴(A) Representative images of the oil red O staining show the accumulation lipid in the liver of differenthistological characteristics of monkeys. (B) Quantification shows the lipid integral optical density.→：Lipid droplets3.1.4 血液生化结果猕猴筛选结束后，统计每组血液生化结果(见表 4)。与正常和患有简单脂肪肝的猕猴相比，患有 NASH 的猕猴的 FPG 和 TG 显著升高（P <0.01），但是 ALB，HDL及 LDL 均在正常范围内。表 4 猕猴血液生化结果Table 4. Biochemical of the Study MonkeysVariables Normal (n =23) Simple steatosis (n = 45) NASH (n = 9)FPG(mmol/L) 4.77±0.54 4.69±0.477 6.27±1.65**LDL(mmol/L) 1.15±0.26 1.33±0.34 1.83±0.82
【参考文献】：
期刊论文
[1]Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy[J]. Maria Nicoline Baandrup Kristiansen,Sanne Skovg?rd Veidal,Kristoffer Tobias Gustav Rigbolt,Kirstine Sloth T?lb?l,Jonathan David Roth,Jacob Jelsing,Niels Vrang,Michael Feigh. World Journal of Hepatology. 2016(16)
[2]Insulin resistance in development and progression of nonalcoholic fatty liver disease[J]. Shahinul Alam,Golam Mustafa,Mahabubul Alam,Nooruddin Ahmad. World Journal of Gastrointestinal Pathophysiology. 2016(02)
[3]肠道菌群对非酒精性脂肪性肝病病变程度的影响[J]. 郑啼婴,李瑜元,聂玉强,曹杰,古维立,杜艳蕾,邱睿睿,周永健. 广州医科大学学报. 2016(01)
[4]Mechanism of action of gypenosides on type 2 diabetes and non-alcoholic fatty liver disease in rats[J]. Qin He,Jin-Ke Li,Fang Li,Ru-Gui Li,Guo-Qing Zhan,Gang Li,Wei-Xing Du,Hua-Bing Tan. World Journal of Gastroenterology. 2015(07)
[5]Non-alcoholic fatty liver disease: What the clinician needs to know[J]. Mariana Verdelho Machado,Helena Cortez-Pinto. World Journal of Gastroenterology. 2014(36)
[6]2型糖尿病合并非酒精性脂肪肝与糖尿病慢性并发症的相关性[J]. 赵新,陈延延,李晓通,耿静,肖金凤,朱铁虹. 中国慢性病预防与控制. 2014(01)
[7]非酒精性脂肪性肝病研究的关切点[J]. 曾民德. 肝脏. 2009(04)
[8]Metabolic syndrome and non-alcoholic fatty liver disease:Asian definitions and Asian studies[J]. Jian-Gao Fan and Yong-De Peng Center for Fatty Liver Disease & Department of Endocrinology, Shanghai First People’s Hospital, Jiaotong University, Shanghai 200080, China. Hepatobiliary & Pancreatic Diseases International. 2007(06)
[9]非酒精性脂肪性肝炎肝组织TNF-α、TGF-β1和Leptin的表达及意义[J]. 丁效蕙,赵景民,孙艳玲,周光德,潘登,杨建法,赵雨来. 解放军医学杂志. 2006(08)
[10]非酒精性脂肪性肝病诊疗指南[J]. Fatty Liver and Alcoholic Liver Disease Study Group of the Chinese Liver Disease Association.. 中华肝脏病杂志. 2006(03)
本文编号：3350580
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