P53正向细胞凋亡调控因子抑制剂对肝脏缺血再灌注损伤的保护作用  

Protective Effect of P53 Upregulated Modulator of Apoptosis Inhibitor on The Hepatic Ischemia-reperfusion Injury

作　　者：王炎[1] 任子健[1] 王荣根[1] 胡菲菲[1] 程俊霖[1,2] 张正卫[1] 杨海元[1] 王盈[1] 余健 戴一凡[1] 

机构地区：[1]南京医科大学江苏省异种移植重点实验室,南京210029 [2]南京医科大学附属南京市第一人民医院,南京210006 [3]Department of Pathology,University of Pittsburgh Cancer Institute [4]University of Pittsburgh School of Medicine,Pittsburgh,PA

出　　处：《生物物理学报》2014年第2期127-136,共10页Acta Biophysica Sinica

基　　金：江苏省异种移植重点实验室经费(BM2012116)~~

摘　　要：P53正向细胞凋亡调控因子(P53 upregulated modulator of apoptosis,PUMA)是Bcl-2家族唯BH3结构域亚家族成员,位于线粒体内,可被多种损伤因素诱导激活。PUMA通过BH3结构域与Bcl-2样抗凋亡蛋白结合后发挥其促凋亡作用。PUMA抑制剂模拟蛋白间的结合作用,阻碍PUMA与Bcl-2样蛋白结合,凋亡被抑制。在体内,依小鼠肝脏缺血、再灌注时间不同,损伤情况各异。损伤较轻时,PUMA表达升高,PUMA抑制剂能够保护肝脏抵抗损伤;当损伤较严重时,PUMA表达升高不明显,PUMA抑制剂的保护作用也不明显。综合上述,在一定程度损伤的条件下,PUMA抑制剂可以有效地保护肝脏,减轻损伤。P53 upregulated modulator of apoptosis （PUMA） is a BH-3-only member of Bcl-2 family. It＇s located in the mitochondrion and remains low expression under normal circumstances. PUMA can be induced by many stimuli, including radiation, virus, chemotherapeutics, et al. PUMA binds Bcl-2-1ike proteins with its particular BH3 domain to inhibit antiapoptosis. PUMA inhibitor mimics these interactions between PUMA and Bcl-2-1ike proteins so that it could interfere the binding. In vivo, mouse hepatic ischemia-reperfusion model was used to determine PUMA expression and the protective effect of PUMA inhibitor on hepatic injury. The authors found that the degree of the liver injury was dependent on the time of ischemia and reperfusion. PUMA expression increased after the minor ischemia-reperfusion injury which could be inhibited by PUMA inhibitor. On the contrary, severing injuries by extending ischemic time did not increase PUMA expression and the PUMA inhibitor has no protective effect on the injury. It is concluded that PUMA inhibitor can effectively reduce certain degree of hepatic injury.

关 键 词：P53正向细胞凋亡调控因子 凋亡 肝脏缺血再灌注 阿霉素 小鼠胚胎成纤维细胞 

分 类 号：R363[医药卫生—病理学]