CAJ | 학술논문

目的：本研究旨在对ob/ob小鼠腹腔注射罗格列酮,观测小鼠空间学习记忆能力及大脑海马组织中与认知功能相关的蛋白表达变化,进而探讨引起这些变化的机制。方法C57BL/6J ♂ ob/ ob 小鼠分两组,一组腹腔注射罗格列酮(RSG),即罗格列酮组(ob/ ob-RSG),一组注射同等体积的生理盐水,即生理盐水组( ob/ ob-Saline),同鼠龄正常 C57BL/6J(WT)♂小鼠为同型对照,即正常组(WT)。饲养7个月后注射药物并连续检测随机血糖10 d,新事物探索实验检测空间学习记忆能力。Western blot 方法检测海马中 BACE1、磷酸化Tau、磷酸化IRS1及IRS1、磷酸化Akt 及Akt 等蛋白的表达水平,ELISA 的方法检测Aβ1-40的水平。结果罗格列酮组小鼠随机血糖水平明显低于生理盐水组,并趋于正常组。新事物探索实验结果显示罗格列酮组的空间学习记忆能力相对于生理盐水组有所改善。罗格列酮组小鼠海马组织中BACE1及磷酸化Tau 的表达水平相对于生理盐水组明显下降,并趋于正常组。类似的,海马组织中Aβ水平在罗格列酮处理后明显下降。罗格列酮组小鼠大脑海马组织中胰岛素信号通路相关蛋白IRS1以及下游Akt 的磷酸化水平相对于生理盐水组均明显增高,并趋于正常组。结论 ob/ ob 小鼠在注射罗格列酮后,海马组织中IRS1/ Akt 胰岛素信号通路被激活进而改善肥胖导致的认知功能障碍。
목적：본연구지재대ob/ob소서복강주사라격렬동,관측소서공간학습기억능력급대뇌해마조직중여인지공능상관적단백표체변화,진이탐토인기저사변화적궤제。방법C57BL/6J ♂ ob/ ob 소서분량조,일조복강주사라격렬동(RSG),즉라격렬동조(ob/ ob-RSG),일조주사동등체적적생리염수,즉생리염수조( ob/ ob-Saline),동서령정상 C57BL/6J(WT)♂소서위동형대조,즉정상조(WT)。사양7개월후주사약물병련속검측수궤혈당10 d,신사물탐색실험검측공간학습기억능력。Western blot 방법검측해마중 BACE1、린산화Tau、린산화IRS1급IRS1、린산화Akt 급Akt 등단백적표체수평,ELISA 적방법검측Aβ1-40적수평。결과라격렬동조소서수궤혈당수평명현저우생리염수조,병추우정상조。신사물탐색실험결과현시라격렬동조적공간학습기억능력상대우생리염수조유소개선。라격렬동조소서해마조직중BACE1급린산화Tau 적표체수평상대우생리염수조명현하강,병추우정상조。유사적,해마조직중Aβ수평재라격렬동처리후명현하강。라격렬동조소서대뇌해마조직중이도소신호통로상관단백IRS1이급하유Akt 적린산화수평상대우생리염수조균명현증고,병추우정상조。결론 ob/ ob 소서재주사라격렬동후,해마조직중IRS1/ Akt 이도소신호통로피격활진이개선비반도치적인지공능장애。
Aim To identify alteration in key molecular components related to memory formation and insulin signaling in the hippocampus after rosiglitazone was in-jected into the ob/ob mice to test whether cognitive dysfunction was pharmacologically reversed by regula-tion of rosiglitazone. Methods The age-matched mice were divided into three groups ( n=18 ): Saline-trea-ted WT mice ( WT-Saline);Saline-treated ob/ob mice ( ob/ob-Saline) and RSG-treated ob/ob mice ( ob/ob-RSG) through intraperitoneal injection of rosiglitazone ( RSG) . The random glucose levels were measured for 10 days during the intraperitoneal injection period. No-vel object recognition was performed before mice were sacrificed. Western blot was implemented to evaluate the following proteins: BACE1, p-Tau, p-IRS1,IRS1, p-Akt and Akt in hippocampal tissues. The Aβ1-40 levels were detected by ELISA Kit. Results The random blood glucose levels were significantly re-duced in ob/ob-RSG compared with ob/ob-saline. RSG treatment led to an increase in hippocampus-de-pendent cognition of ob/ob mice according to the novel object recognition. The proteins levels of BACE1, p-Tau and Aβ were lowered in RSG-treated ob/ob mice. Furthermore, RSG treatment up-regulated hippocampal p-IRS1/IRS1 and p-Akt/Akt ratio. Conclusion Ros-iglitazone ameliorates cognitive deficits in ob/ob mice through up-regulating insulin signaling pathways in the hippocampus.