项目名称: 青藤碱对LPS诱导ICAM-1高表达的干预机制研究
项目编号: No.31502112
项目类型: 青年科学基金项目
立项/批准年度: 2016
项目学科: 水产学、兽医学
项目作者: 胡屹屹
作者单位: 江苏省农业科学院
项目金额: 21万元
中文摘要: 兽医临床上细菌内毒素引起的疾病,起病急速,进展迅速,病情凶险,病死率高,严重制约我国畜牧产业的健康发展。我们前期从六种中药生物碱成分中,筛选出抗内毒素效果显著的药物青藤碱。细胞间黏附分子-1(ICAM-1)在炎症、发热、凝血、休克等内毒素诱发的病理过程中起关键作用。本项目拟以内毒素诱导猪血管内皮细胞高表达ICAM-1为病理模型,首先从细胞分泌、蛋白翻译和转录水平,逐步深入研究青藤碱对ICAM-1不同阶段表达的影响,明确药时关系。其次观察青藤碱对ICAM-1信号传导通路上的关键节点ERK1/2、p38、SAPK/JNK和NF-κB的阻抑作用,解析药物的干预过程。然后采用高通量的全基因组芯片检测技术,通过差异基因表达情况分析青藤碱抗内毒素的具体机制。最后通过靶动物体内试验,进一步细化证实青藤碱的抗内毒素功效,旨在为兽医临床细菌疫病的防控和中兽药制剂的系列研发提供理论依据。
中文关键词: 内毒素;青藤碱;细胞间黏附分子-1;血管内皮细胞;炎症
英文摘要: The bacterial endotoxin diseases are acute onset, rapid progress, serious illness and high mortality rate in veterinary clinic. We screened out significant effect drug sinomenine for antiendotoxin from six alkaloids of traditional Chinese medicine in previous trials. Intercellular cell adhesion molecule-1 (ICAM-1) play important roles in a number of physiological and pathological processes, such as inflammation, fever, coagulation and shock. The endotoxin induces vascular endothelial cells with high expression of ICAM-1 for pathological model of this project. Firstly we want to investigate the expression of ICAM-1 induced by LPS and/or sinomenine from the levels of cell, protein and transcription. Then ICAM-1 signal transduction pathway will be detected by protein content for phosphorylated and total of ERK1/2, p38, SAPK/JNK. The intervention process of sinomenine for antiendotoxin will be analyzed by activity of NF-κB. The specific mechanisms of sinomenine for antiendotoxin will be interpreted by differentially expressed genes from whole-genome microarray. Lastly the pharmacological effect of sinomenine will be proved by a number of indication in target animal pigs. All these research will provide the theoretical basis for prevention and control of bacterial diseases in veterinary clinic, as well as research and development of the Chinese traditional veterinary medicine.
英文关键词: Endotoxin;Sinomenine;ICAM-1;VEC;Inflammation