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中文摘要：
肝硬化门脉高压是常见的、我国最严重的公共卫生问题之一。我们前期研究提示，门脉高压时肝内滞留的生长抑素（SST）极有可能改变肝细胞的增殖周期，诱导其凋亡；促进肝细胞细胞向间质细胞转变，导致纤维化；恰当时机的门体分流有助于保护残存的肝细胞，维持肝功能。本项目拟从门脉高压这一探索不多的角度，从SST的角度探讨肝窦型门脉高压对肝细胞凋亡、修复及再生的分子、细胞生物学变化。本研究对象以肝细胞为主体，致病因素主要为门脉高压，肝细胞内的分子事件以多胺代谢为枢纽，观察的细胞转归涉及凋亡、再生及上皮-间质转化。研究思路来自临床，所证实的结果将为临床门体分流时机提供理论依据，为改善肝硬化患者干细胞移植的效果提供新思路，体现了临床与实验室的双向转换。
英文摘要：
Liver cirrhosis；Portal hypertension；Somatostatin；Epithelial-Mesenchymal Transition；Angiogenesis
结论摘要：
肝硬化门脉高压是常见的、我国最严重的公共卫生问题之一。门脉高压作为慢性肝病整个病程中的第二次打击，其加速肝细胞凋亡及纤维化的机制则十分令人感兴趣。我们前期研究提示，门脉高压时肝内滞留的生长抑素（SST）极有可能改变肝细胞的增殖周期，诱导其凋亡；促进肝细胞细胞向间质细胞转变，导致纤维化；恰当时机的门体分流有助于保护残存的肝细胞，维持肝功能。本项目研究结果显示奥曲肽可以缓解TAA诱导的肝硬化和门静脉高压。这些缓解作用和奥曲肽可以抑制肝细胞EMT、肝脏炎症、肝血窦内皮细胞毛细血管化和肝内肝外血管新生，促进间质细胞凋亡凋亡有关。奥曲肽可以通过调节SST-SSTRs通路、TGF-b1-Smad通路和MAPK-ERK通路从而发挥其治疗肝硬化和门静脉高压的作用。由于SST是人体内源性调节多肽，SST类似物奥曲肽已应用于胃食管静脉曲张出血的临床治疗，因此本研究的结果有望快速进行转换医学将其应用于肝硬化门静脉高压病人的临床治疗中。在本项目经费的支持下，本研究团队累计发表SCI论文28篇，Medline及国内核心期刊5篇。所有发表论文均已标注受Natural Science Fund of China资助，其中9篇论文标注Natural Science Fund of China (81170413)。研究成果在国际顶级学术会议（美国胃肠疾病周和欧洲消化年会）进行大会发言交流6次，壁报交流13次。有28人次在中华医学会消化疾病年会中进行发言交流展示本研究团队研究成果。项目负责人以主编或副主编身份编著论著6部，培养2名博士后，9名博士研究生，1名硕士研究生，并获得四川省科技进步一等奖一项。
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期刊论文
Small-for-Size syndrome after living donor liver transplantation: successful treatment with a transj
Somatostatin and octreotide on the treatment of acute pancreatitis --- basic and clinical studies fo
Octreotide alleviates obesity by reducing intestinal glucose absorption and inhibiting low-grade inf
[The Expressions of Somatostatin and Cycloxygenase-2 in Chronic Hepatitis, Hepatic Cirrhosis, Precan
Combinative treatment of transarterial chemoembolization, celecoxib and lanreotide in unresectable h
Role of mesenteric lymph pathway in the effects of exogenous somatostatin against early intestinal i
Recurrent variceal bleeding and shunt patency: prospective randomized controlled trial of transjugul
Prevention of severe acute pancreatitis with octreotide in obese patients: A prospective multi-cente
Transcatheter arterial embolization followed by octreotide and celecoxib synergistically prolongs su
High-dose versus low-dose octreotide in the treatment of acute pancreatitis: a randomized controlled
Acute ethanol administration inhibits Toll-like receptor 4 signaling pathway in rat intestinal epith
Targeting inhibition of extracellular signal-regulated kinase kinase pathway with AZD6244 (ARRY-1428
Compound heterozygous mutations of ABCB11 responsible for benign recurrent intrahepatic cholestasis.
Celecoxib attenuates hepatic cirrhosis through inhibition of epithelial-to-mesenchymal transition of
Somatostatin Inhibits the Production of Interferon-gamma by Intestinal Epithelial Cells During Intes
会议论文
Octreotide attenuates hepatic fibrogenesis and portal hypertension in the TAA induced cirrhotic rats
Transarterial chemoembolization with celecoxib and lanreotide in treatment of hepatocellular carcino
Effect of Long-Term Alcohol Intake on Pancreatic Fat Content in Humans -Characteristics of Alcohol-I
Attenuation of Hepatic Fibrogenesis and Portal Hypertension in the Cirrhotic Rats With Celecoxib and
Oral Feeding Versus Nasogastric Feeding in Predicted Severe Acute Pancreatitis: A Randomized Clinica
A Prospective Evaluation of Multi-Factors on the Efficacy of Transjugular Intrahepatic Portosystemic
Hepatic expression of somatostatin receptor 2 may be regulated by cyclooxygenase-2 in a rat model of
Life-threatening GI hemorrhage caused by pulmonary vein-esophagealfistula: a rare complication after
Octreotide and Celecoxib Synergistically Ameliorate Portal Hypertension of the Cirrhotic Rats Throug
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