南方医科大学学报
南方醫科大學學報
남방의과대학학보
Journal of Southern Medical University
2015年
8期
1162-1165
,共4页
舒林酸%孤独症%Wnt信号通路
舒林痠%孤獨癥%Wnt信號通路
서림산%고독증%Wnt신호통로
sulindac%autism%Wnt signaling pathway
目的 探讨舒林酸对孤独症模型大鼠病症行为的改善作用.方法 在大鼠怀孕12.5 d后采用一次性腹腔注射丙戊酸钠(VPA)制备孤独症大鼠模型.针对舒林酸处理组,于VPA注射后每天给大鼠口服20 mg/kg舒林酸直至断奶.将出生幼鼠分为4组:对照组,VPA处理组,舒林酸处理组及VPA联合舒林酸处理组.出生后35 d对幼鼠进行社会交往行为检测、敞箱焦虑样行为检测,并分离提取脑组织蛋白利用Western blot分析Wnt信号通路关键蛋白β-catenin与Gsk3β表达情况.结果 成功制备孤独症大鼠模型.与对照组相比,VPA处理组社会交往能力下降、在中央区活动时间增加、站立次数减少,符合孤独症行为特征;舒林酸单独处理组无明显行为学变化;但舒林酸联合处理能明显改善VPA处理导致的孤独症行为症状.Western blot结果显示,与对照组相比,VPA处理可增强大鼠前额叶、海马及小脑组织中β-catenin表达水平并降低Gsk3β第9位丝氨酸磷酸化水平;而舒林酸联合处理则能抑制上述脑组织中β-catenin表达水平并增加Gsk3β第9位丝氨酸磷酸化水平.结论 舒林酸可改善孤独症模型大鼠的病症行为,机制可能与抑制脑组织中Wnt信号通路相关.
目的 探討舒林痠對孤獨癥模型大鼠病癥行為的改善作用.方法 在大鼠懷孕12.5 d後採用一次性腹腔註射丙戊痠鈉(VPA)製備孤獨癥大鼠模型.針對舒林痠處理組,于VPA註射後每天給大鼠口服20 mg/kg舒林痠直至斷奶.將齣生幼鼠分為4組:對照組,VPA處理組,舒林痠處理組及VPA聯閤舒林痠處理組.齣生後35 d對幼鼠進行社會交往行為檢測、敞箱焦慮樣行為檢測,併分離提取腦組織蛋白利用Western blot分析Wnt信號通路關鍵蛋白β-catenin與Gsk3β錶達情況.結果 成功製備孤獨癥大鼠模型.與對照組相比,VPA處理組社會交往能力下降、在中央區活動時間增加、站立次數減少,符閤孤獨癥行為特徵;舒林痠單獨處理組無明顯行為學變化;但舒林痠聯閤處理能明顯改善VPA處理導緻的孤獨癥行為癥狀.Western blot結果顯示,與對照組相比,VPA處理可增彊大鼠前額葉、海馬及小腦組織中β-catenin錶達水平併降低Gsk3β第9位絲氨痠燐痠化水平;而舒林痠聯閤處理則能抑製上述腦組織中β-catenin錶達水平併增加Gsk3β第9位絲氨痠燐痠化水平.結論 舒林痠可改善孤獨癥模型大鼠的病癥行為,機製可能與抑製腦組織中Wnt信號通路相關.
목적 탐토서림산대고독증모형대서병증행위적개선작용.방법 재대서부잉12.5 d후채용일차성복강주사병무산납(VPA)제비고독증대서모형.침대서림산처리조,우VPA주사후매천급대서구복20 mg/kg서림산직지단내.장출생유서분위4조:대조조,VPA처리조,서림산처리조급VPA연합서림산처리조.출생후35 d대유서진행사회교왕행위검측、창상초필양행위검측,병분리제취뇌조직단백이용Western blot분석Wnt신호통로관건단백β-catenin여Gsk3β표체정황.결과 성공제비고독증대서모형.여대조조상비,VPA처리조사회교왕능력하강、재중앙구활동시간증가、참립차수감소,부합고독증행위특정;서림산단독처리조무명현행위학변화;단서림산연합처리능명현개선VPA처리도치적고독증행위증상.Western blot결과현시,여대조조상비,VPA처리가증강대서전액협、해마급소뇌조직중β-catenin표체수평병강저Gsk3β제9위사안산린산화수평;이서림산연합처리칙능억제상술뇌조직중β-catenin표체수평병증가Gsk3β제9위사안산린산화수평.결론 서림산가개선고독증모형대서적병증행위,궤제가능여억제뇌조직중Wnt신호통로상관.
Objective To test the effect of sulindac on autistic behaviors in a rat model and explore the possible mechanisms. Methods Autistic rat models were established by a single intraperitoneal injection of sodium valproate (VPA) at 12.5 days of pregnancy. The pregnant rats were treated with oral sulindac at a daily dose of 80 mg/kg until weaning of the newborn rats (23 days after being born), which were divided into control, VPA treatment, sulindac treatment, and VPA+ sulindac treatment groups. The social interaction and neuroethology of the newborn rats were evaluated at 35 days, and the levels of β-catenin and phosphorylated Gsk3βin the brain tissues were investigated by Western blotting. Results Compared with the control rats, the rats treated with VPA showed lower social interaction, longer moving time in central area, and reduced standing times. Treatment with sulindac alone resulted in no obvious changes in the social interaction or neuroethology of the newborn rats, but sulindac treatment corrected VPA-induced autistic-like behaviors. Sulindac also attenuated VPA-triggered p-Gsk3βdownregulation andβ-catenin upregulation in the prefrontal lobe, seahorse and cerebellum. Conclusion Sulindac can improve the behaviors of autistic rats possibly by suppressing Wnt signaling pathway.
