裸鼹鼠抵抗病毒感染相关机制的初步研究  

Preliminary Study on Mechanism of Antiviral Effect in Naked Mole Rat

作　　者：肖邦[1] 赵善民[1] 林丽芳[1] 王运慧[1] 宫晨[1] 余琛琳[1] 张璐[1] 汤球[1] 孙伟[1] 崔淑芳[1] 

机构地区：[1]第二军医大学实验动物中心,上海200433

出　　处：《实验动物与比较医学》2014年第5期422-427,共6页Laboratory Animal and Comparative Medicine

基　　金：国家自然科学基金项目（No.31402028）,上海市科技发展基金项目（No.12140900200）与（No.13140900400）联合资助

摘　　要：目的 探讨多聚肌苷-多聚胞苷酸钠盐（PolyI∶C）诱导下裸鼹鼠肺脏、肠组织的病理变化以及低氧诱导因子（HIF-1 α）和坏死因子（NF-κB）信号通路关键基因的表达水平,分析裸鼹鼠抵抗病毒可能的分子机制.方法 裸鼹鼠分为PolyI∶C处理组、生理盐水对照组.注射12h后处死动物,肺脏和肠组织切片经HE染色后观察病理变化;提取裸鼹鼠肺脏、肠组织中mRNA,采用半定量RT-PCR方法检测基因HIF-1 α、VEGFb（血管内皮生长因子b）、VEGF c（血管内皮生长因子c）、FLT-1（血管内皮生长因子受体1）、Fiz1（血管内皮生长因子受体3结合锌指蛋白1）、NKRF（转录因子NRF蛋白）的表达水平.结果 与对照组相比,PolyI∶C处理组的肺脏和肠组织病理变化不明显,而所检测基因的表达水平几乎都显著下降,仅肠组织中的FIZ1的表达水平有所上升（P＞0.05）.结论 PolyI∶C对裸鼹鼠没有产生明显的致病作用,它不能诱导裸鼹鼠体内HIF-1α和NF-κB信号通路活化,提示裸鼹鼠可能通过抑制相关信号通路的活性促使体内受感染的靶细胞迅速凋亡,从而清除入侵的病原体.Objective To explore the pathologic changes of lung and gut of naked mole rats and theexpression level of key genes of HIF-1α and NF-κB signaling pathways induced by Polyinosine-pdycytidylic acid （PolyI： C） for analyzing the possible mechanism of resistence to virus in naked mole rats. Methods The naked mole rats were divided into PolyI： C treatment group and co＇ntrol group （injected with normal saline）. The animals were sacrificed 12 h later, and then the pathological changes of lung and gut tissue were observed. Total mRNA of lung and gut of the naked mole rats were extracted and the expression level of HIF-lo; VEGFb, VEGFc, FLT-1, Fizl, NKRF were detected by RT-PCR. Results There is no difference in the pathological changes of lung and gut tissue between the PolyI： C treatment group and control group. The expression level of HIF-1α, VEGFb, VEGFc, FLT-1, NKRF detected were decreased significantly in treatmeat group, but the expression levels of FIZ1 in intestinal tissue increased compared to that of the control group, though the difference is not significant. Conclusion PolyI： C can not lead to obvious pathogenic changes in naked mole rats, and it can inhibit the activation of HIF-1 and NF-κB signaling pathway in naked mole rats. the naked mole rats possibly inhibit the activity of signaling path- ways to lead to the apoptosis of cell infected with virus to eliminate the invaded pathogens.

关 键 词：裸鼹鼠 多聚肌苷-多聚胞苷酸钠盐(PolyI∶C) 信号通路 HIF-1Α NF-ΚB 

分 类 号：R-332[医药卫生]