【摘要】 目的观察孕前慢性皮质酮诱导产后抑郁(PPD)模型小鼠行为改变及其分子机制。方法C57BL/6N母鼠进行皮质酮注射,造模4周,然后与正常公鼠交配,分娩后分为空白组和孕前皮质酮诱导组,于造模4周和分娩3周时进行行为学测试。蛋白免疫印迹法(Western blot)检测小鼠海马中蛋白激酶B(AKT)、雷帕霉素靶蛋白(m TOR)总蛋白及磷酸化蛋白的表达。结果小鼠造模后和产后体重均明显下降(P<0.01),悬尾测试不动时间(TST)均显著增加(P<0.01);强迫游泳测试(FST)结果中模型组小鼠在造模4周时不动时间明显增长(P<0.01),产后3周时无明显差异(P>0.05);陌生环境摄食测试结果中模型组首次进食潜伏时间显著增加(P<0.01),在摄食总量上,造模4周时明显下降(P<0.01),产后3周时无明显差异(P>0.05)。Western blot结果显示,模型组小鼠海马中总AKT、总mTOR蛋白表达无明显变化(P>0.05),p-AKT(P<0.05)、p-mTOR(P<0.01)表达显著下降。结论慢性皮质酮孕前注射可诱导C57BL/6N小鼠出现产后抑郁表型,其发病机制可能与AKT-mTOR信号通路活性下降有关。更多还原

【Abstract】 Objective To investigate the depressive behavioral pattern and molecular mechanisms in pre-pregnancy chronic corticosterone(CORT)-induced postpartum depression(PPD) mice. Methods Female C57BL/6 N mother mice were administrated with hypodermic CORT,4 weeks later they were mating with normal male mice,and then were divided into control group(Con) and pre-pregnancy CORT-induced group(Mod) at postpartum. Behavioral tests were performed at 4 weeks after administration and 3 weeks after postpartum. The expression levels of AKT and mTOR total protein as well as their phosphorylated protein were detected by Western-blot. Results The weight of the mice was notably decreased while the immobility times of the TST significantly increased after CORT administration. In the FST,the immobility times of mice also apparently increased after 4 weeks administrated but there was no significant difference at postpartum after 3 weeks. The latency to feed in the NSF were similar to TST and the total food intake in 10min were similar to FST. There was no significant changes in the expression of total AKT or mTOR protein after treatment,however,their phosphorylated protein were down-regulated conspicuously. Conclusion Pre-pregnancy chronic CORT can induce PPD in C57BL/6 N mice,and its pathogenesis is probably associated with the deficit of AKT-mTOR signaling pathway.更多还原