目的 应用细胞因子寡核苷酸表达谱芯片检测血虚小鼠不同脏器组织内造血相关细胞因子差异表达情况 ,寻找差异表达基因 ,为血虚证治疗药物机制研究及治疗药物筛选奠定基础。方法 采用 5 .5 Gy6 0 Co- γ射线照射Balb/c小鼠 ,制备血虚模型。在不同时间点提取正常和血虚小鼠不同组织总 RNA,反转录成不同荧光标记的c DNA探针 ,与表达谱芯片进行杂交 ,对扫描数据进行分析获得血虚小鼠造血相关细胞因子基因的差异表达情况。结果 在各组织中共发现 2 1个差异表达的基因。这些基因的功能大致分为 3类 :促细胞生长或增殖 ,免疫调节 ,诱导血细胞形成或促造血祖细胞形成集落。结论 照射后上述细胞因子基因的下调 ,使机体的造血功能下降 ,造成血虚 ,证明细胞因子间形成造血调节网络 ,整体调节机体造血。这与中医的全局理论是一致的。实验证明应用芯片技术 ,从分子水平研究血虚形成的机制是可行的 ,可为进一步的血虚证治疗药物的筛选提供依据

In the liver, glucokinase (GCK) facilitates hepatic glucose uptake during hyperglycemia and is essential for the regulation of a network of glucose-responsive genes involved in glycolysis, glycogen synthesis, and lipogenesis. To better understand the consequences of changes in response to a liver-specific deficiency of GCK function, we examined the expression profiles of genes involved in glucose metabolism in the liver, pancreas, muscle and adipose tissue in heterozygous liver-specific Gck knockout (Gck(w/-)) mice. Our results showed that with the development of a liver GCK deficiency, significant decreases in the mRNA levels for insulin receptor and Glut2 were observed in the liver, and HkII in muscle, while glucagon mRNA increased markedly in the pancreas. The levels of circulating glucagon hormone levels increased with increased mRNA levels. Depite a decrease in muscle HkII levels, the hexokinase activity level did not change. Our findings suggest that in liver-specific Gck(w/-) mice, peripheral tissues use different strategies to tackle with hyperglycemia even at a young age. By identifying the specific changes that occur in different tissues at an early stage of glucokinase deficiency, potentially we can develop interventions to prevent further progression to diabetes.

全军医药卫生科研基金课题(0 1Z0 19) 北京市科委资助项目(H0 10 2 10 2 2 0 113 )