JNK抑制剂D-JNKI1减少APPswe转基因小鼠的β淀粉样沉积  

JNK inhibitor D-JNKI1 reduced amyloid deposition in APPswe transgenic mice

作　　者：王子钧 辛娜[1] 董玲 解景伟 WANG Zi-jun;XIN Na;DONG Ling;XIE Jing-wei(Department of Pathophysiology,College of Basical Medicine Science,China Medical University,Shenyang 110122,China)

机构地区：[1]中国医科大学基础医学院病理生理学教研室,辽宁沈阳110122

出　　处：《解剖科学进展》2021年第2期129-133,共5页Progress of Anatomical Sciences

基　　金：辽宁省高等学校基本科研项目(LFWK201714);辽宁省自然科学基金(20180551191)。

摘　　要：目的探讨腹腔注射JNK抑制剂D-JNKI1对APPswe转基因小鼠β淀粉样沉积的影响。方法 3月龄APPswe转基因小鼠分为D-JNKI1(11mg/kg)组和生理盐水组,每组6只,分别接受腹腔注射D-JNKI1及等体积生理盐水,持续9个月,免疫组化染色法观察大脑皮层和海马中Aβ的沉积,Western blot法观察大脑皮层和海马APPT668磷酸化水平及APP代谢产物sAPPα和sAPPβ水平、APP分泌酶表达水平、MAPK通路蛋白表达及磷酸化水平和Tau蛋白磷酸化水平。结果在APPswe转基因小鼠大脑皮层和海马中,D-JNKI1使Aβ的沉积减少,pAPPT668水平降低,sAPPβ/sAPPα比值降低,p-JNK、p-c-Jun水平降低,ADAM10、BACE1、PS1表达水平无明显改变,p-Tau水平无明显改变。结论腹腔注射D-JNKI1减少APPswe转基因小鼠大脑皮层和海马的β淀粉样沉积,与抑制JNK活性,从而降低APP磷酸化,进而导致Aβ产生减少相关。Objective To investigate the effect of intraperitoneal injection of JNK inhibitor D-JNKI1 on the β-amyloid deposition of APPswe transgenic mice. Methods 3 month-old APPswe transgenic mice were divided into DJNKI1(11 mg/kg) group and saline group, 6 mice in each group. The mice were accepted intraperitoneal injection of DJNKI1 or equal volume of normal saline per 3 weeks for 9 months, respectively. Immunohistochemical staining was used to observe Aβ deposition in the cerebral cortex and hippocampus. Western blot was used to observe levels of p-APPT668 and APP products(sAPPα and sAPPβ), expression levels of APP secretases, levels of p-MAPK and p-Tau protein in cerebral cortex and hippocampus. Results In cerebral cortex and hippocampus, D-JNKI1 downregulated Aβ deposition, pAPPT668, the ratio of sAPPβ/sAPPα, p-JNK and p-c-Jun levels, but with not effect for ADAM10, BACE1,PS1 and pTau. Conclusion D-JNKI1 reduced amyloid deposition in APPswe transgenic mice, which is related to D-JNKI1 inhibiting JNK pathway, leading to the decreased p-APPT668, resulting in the reduced production of Aβ.

关 键 词：D-JNKI1 MAPK信号通路 β淀粉样沉积 APPswe转基因小鼠 

分 类 号：R593.22[医药卫生—内科学]