CRMP2衍生的ST2-104多肽对阿尔茨海默病大鼠皮质神经元的保护作用  

The protective effects of ST2-104 peptide derived from CRMP2 on cortical neurons in Alzheimer rats

作　　者：孟盼盼[1] 张雨晴[1] 高媛媛[1] 孙莉[2] 李琦[1] 

机构地区：[1]吉林大学基础医学院,吉林长春130021 [2]吉林大学白求恩第一医院神经内科,吉林长春130021

出　　处：《中风与神经疾病杂志》2016年第3期203-206,共4页Journal of Apoplexy and Nervous Diseases

基　　金：吉林省人才开发资金资助项目(No.802150021426);国家自然科学基金(No.81571231)

摘　　要：目的研究ST2-104肽对阿尔茨海默病(AD)大鼠脑皮质内NMDAR1、NMDAR2B、CRMP2、PCRMP2的表达影响,进而改善大鼠的认知功能,对神经元发挥保护作用。方法采用单次单侧脑室微量注射Aβ25-35片段制备AD大鼠模型,具有相同遗传背景的Wistar大鼠作为假手术对照组,分别给予不同剂量的ST2-104多肽和盐酸美金刚治疗。Aβ注射2 d后给药10 d,HE染色法观察脑皮质部分形态变化,甲醇刚果红染色法观察淀粉样物质沉积情况,WB及免疫组化法检测大鼠脑皮质组织NMDAR1、NMDAR2B、CRMP2、P-CRMP2的表达。结果与假手术组相比,模型组淀粉样物质沉积明显增多,脑皮质部分NMDAR2B表达显著增多(P<0.01),NMDAR1表达相对减少,P-CRMP2与CRMP2表达量均无明显差异;ST2-104多肽可以逆转上述现象,降低NMDAR2B表达(与模型组相比,高剂量组P<0.05),增加NMDAR1表达(与模型组相比,高、低剂量均为P<0.05)。结论 (1)ST2-104可能通过减少NMDAR2B表达降低其活性来发挥对AD大鼠皮质神经元的保护作用。Objective To explore the effect of ST2-104 peptide on the expression of NMDAR1,NMDAR2 B,CRMP2and P-CRMP2 in pallium,to elucidate mechanism of ST2-104 on improving the cognitive function following Alzheimer rats.Methods Single single intracerebroventricular microinjection of Aβ25-35 was used to establish the model of Alzheimer and Wistar rats were used as the sham group. Then they were given different dose of ST2-104 or memantine. Administration for10 days after 2 days injection. The change of pallium cells in cortex region was observed by HE staining. Amyloid deposition was observed by ameliorated Highman Congo red staining. Relative NMDAR1,NMDAR2 B,CRMP2,P-CRMP2 ＇s expression were performed by immunohistochemistry and western blot. Results TThere were more amyloid deposition,more NMDAR2 B expression（ P〈0. 01）,less NMDAR1 expression in the model group compared with sham group,but there was no markedly differences between P-CRMP2 and CRMP2＇s expression. ST2-104 peptide could reverse this phenomenon by decreasing the expression of NMDAR2B（ high-dose group,P〈0. 05） and increasing the expression of NMDAR1 expression（ low-dose group and high-dose group,P〈0. 05） compared with the model group. Conclusion ST2-104 peptide might protect neurons from A-beta toxicity by inhibiting the expression of NMDAR2 B and decreasing its activity.

关 键 词：阿尔茨海默病 ST2-104 AΒ25-35 NMDAR CRMP2 

分 类 号：R749.16[医药卫生—神经病学与精神病学]