糖尿病大鼠海马神经元存活和凋亡相关蛋白的表达及APP17肽的作用  

Effect of APP17 peptide on modulating the neur onal apoptosis-related proteins in the hippocampus of STZ-DM rats

作　　者：李红星[1] 赵志炜[1] 王蓉[1] 姬志娟[1] 盛树力[1] 

机构地区：[1]首都医科大学宣武医院北京脑老化研究实验室

出　　处：《中华糖尿病杂志（1006-6187）》2004年第5期369-372,共4页

基　　金：国家科技部 973课题资助项目 (G2 0 0 0 0 5 70 10 )

摘　　要：目的　探讨糖尿病 (DM )大鼠海马神经元存活和凋亡相关蛋白神经生长因子α(NGF)、I抗磷脂酰肌醇 3激酶 (PI 3K)、有丝分裂原活化蛋白激酶 (MAPK)、凋亡诱导因子 (AIF)、细胞色素C和磷酸化 MAPK的表达以及APP17肽的作用。　方法　用链脲佐菌素腹腔注射诱发DM模型 ,并皮下注射APP17肽对DM大鼠进行治疗。 12周后 ,6只大鼠取脑组织行NGF、PI 3K、MAPK和AIF、细胞色素C抗体的免疫组化染色 ;6只取新鲜海马组织匀浆 ,以免疫沉淀并Western印迹方法检测PI 3K及磷酸化MAPK抗体的表达。　结果　DM组大鼠海马CA1区NGF、PI 3K、MAPK表达减少(P <0 0 1) ,AIF、细胞色素C阳性神经细胞增多 (P <0 0 1) ;APP17肽治疗 (DP)组与DM组比较 ,AIF(P <0 0 5 ) ,NGF、PI 3K、MAPK和细胞色素C的表达差异有显著意义 (P <0 0 1) ,接近正常对照(NC)组。Western印迹法显示DM组PI 3K比NC组降低 ,p MAPK的表达 3组无明显区别 ;DP组与DM组比较PI3 K表达增高。　结论　DM大鼠海马神经细胞存在功能异常 ,神经存活和凋亡蛋白的异常改变可能参与DM脑病的发生发展 ;Objective To investigate the alteration of appo to sis-related proteins in hippocampal neurons of STZ-DM rats and the possible ef fect of APP-17 peptide on the proteins. Methods Male Wistar diabetic rats were made by STZ. The APP-17 peptide-treated rats were injected with APP-17 peptide three times a week, whereas the control and DM groups were given normal saline. At the 13th week when the animals were terminated, protei ns such as NGF,PI-3K,MAPK, AIF(apoptosis- inducing factor),cytochrome C and p-MAPK were detected by the immunohistochemisty and Western blot. Results The positive rates of NGF, PI-3K and MAPK immune-reactive n eurons in DM group were less than those in the normal and APP-17-treated group significantly(P<0.01). However, AIF and cytochrome C-positive neurons we re widely distributed in hippocampus of DM group (P<0.01). The level of PI-3K protein in DM group was less than that of the control and APP-17 pept ide-treated group, whereas the expression of p-MAPK showed no difference among the three groups. Conclusions APP-17 peptide, as a neur oprotective fragment, can significantly reverse the expression of some apoptosis - related proteins, thus facilitating the neuronal survival pathway-related proteins. Abnornal expression of some proteins related to neuronal apoptotic a nd survival pathway might contribute to the mechanism of diabetic enc ephalopathy. APP-17 peptide plays an anti-apoptosis role in it.

关 键 词：APP17肽 DM MAPK 表达 NGF 凋亡相关蛋白 大鼠海马 治疗 细胞色素C 糖尿病大鼠 

分 类 号：R587.1[医药卫生—内分泌] R735[医药卫生—内科学]