论文部分内容阅读
目的 IL 1可诱导内皮细胞粘附分子表达 ,促进缺血部位炎症和局部细胞损伤 ,应用腺病毒介导IL 1ra基因观察其对小鼠局灶性脑缺血后内皮细胞ICAM 1蛋白表达的抑制作用。方法 构建携带外源性基因、复制缺陷的人腺病毒 ,并将其作为载体介导IL 1ra基因、EcoliLacZ基因或以生理盐水分别注射于成年CD 1小鼠右侧脑室。 5d后 ,对实验小鼠分别进行脑血管腔内栓塞术 ,造成持续性中动脉栓塞 ,缺血程度由激光多普勒流量仪确定。采用组织病理切片观察病灶部位白细胞浸润和炎症反应现象 ,免疫组化染色测定血管内皮细胞ICAM 1蛋白表达和用Western印迹进行定量分析。结果 病灶侧皮质区血管内皮细胞ICAM 1蛋白表达量在IL 1ra基因组有明显下降且局部炎症反应轻微 ,与LacZ基因组和生理盐水组比较差异有显著性。ICAM 1蛋白定量分析表明 ,前组比后两组下降 5 0 %左右。但正常侧和病灶侧的脑基质神经节区无明显差异。结论 IL 1ra基因表达蛋白通过抑制IL 1的生物学功能 ,明显下调脑缺血皮质区ICAM 1蛋白表达 ,有助于减轻局部炎症。
Objective IL 1 can induce the expression of endothelial cell adhesion molecule, promote the inflammation of ischemia site and local cell injury. Using adenovirus mediated IL 1ra gene to observe its inhibitory effect on ICAM 1 protein expression in endothelial cells after focal cerebral ischemia in mice effect. Methods Human adenovirus carrying exogenous gene and replication defect was constructed and used as a vector to mediate IL 1ra gene, EcoliLacZ gene or normal saline into the right ventricle of adult CD 1 mice. After 5 days, the experimental mice were subjected to intracavitary endovascular embolization, resulting in persistent arterial embolism, the degree of ischemia was determined by laser Doppler flowmeter. The leukocyte infiltration and inflammatory reaction were observed by histopathological sections. The expression of ICAM 1 protein in vascular endothelial cells was detected by immunohistochemistry and quantified by Western blotting. Results ICAM 1 protein expression in vascular endothelial cells in the lesion side of the lesion was significantly decreased in the IL 1ra genome and local inflammatory response was slight, which was significantly different from LacZ genome and saline group. ICAM 1 protein quantitative analysis showed that the former group than the latter two groups decreased about 50%. However, there was no significant difference in the brain stromal ganglion between normal and lesioned sides. Conclusion IL-1ra gene expression protein can down-regulate the expression of ICAM-1 protein in cerebral ischemic cortex by inhibiting the biological function of IL-1, which may help to reduce the local inflammation.