Akt信號通路在非典型性抗精神病藥物阿立哌唑調節(jié)海馬神經細胞凋亡中的作用
發(fā)布時間:2018-04-25 15:39
本文選題:阿立哌唑 + Akt信號通路。 參考:《中國老年學雜志》2017年09期
【摘要】:目的探討非典型性抗精神病藥物阿立哌唑是否通過Akt信號通路對海馬神經細胞的凋亡發(fā)揮作用。方法通過構建精神分裂癥(CPZ)模型小鼠,設置對照組、阿立哌唑組、CPZ組、CPZ+阿立哌唑四組,實驗結束后對小鼠斷頭取腦,冰上分離出海馬組織和脊髓,培養(yǎng)海馬神經細胞,流式細胞儀檢測細胞凋亡情況,MTT檢測細胞增殖、Western印跡檢測自噬相關蛋白Beclin1的表達情況;使用磷酸化Akt信號通路試劑盒對總Akt,磷酸化Akt(Ser473)含量的變化情況進行檢測。結果對飼養(yǎng)6 w后的小鼠提取海馬神經細胞,流式細胞儀、MTT檢測結果表明,建立CPZ模型的小鼠,在飼養(yǎng)過程中使用阿立哌唑能明顯降低海馬神經細胞的凋亡率;MTT檢測結果表明,與對照組相比,使用阿立哌唑的CPZ模型小鼠海馬神經細胞的存活率明顯提高(P0.01);Western印跡檢測自噬相關蛋白Beclin1的結果表明,構建的CPZ模型小鼠脊髓受到一定程度損傷,Beclin1的表達量明顯升高(P0.01),給阿立哌唑后其表達量顯著下降;在CPZ組中總Akt及Ser473的表達水平均顯著下降(P0.01),通過服用阿立哌唑后表達水平出現(xiàn)回升,與對照組相比差異不顯著(P0.05)。結論非典型性抗精神病藥物阿立哌唑可通過Akt信號通路使海馬神經細胞免于凋亡。
[Abstract]:Aim to investigate whether aripiprazole, an atypical antipsychotic drug, plays an important role in hippocampal neuronal apoptosis through Akt signaling pathway. Methods the model mice with schizophrenia (CPZ) were set up as control group and aripiprazole group (CPZ group) as CPZ group. After the experiment, hippocampus and spinal cord were isolated and hippocampal nerve cells were cultured. Apoptosis was detected by flow cytometry and the expression of autophagy associated protein (Beclin1) was detected by Western blotting, and the changes of total Akt, phosphorylated Aktfen Ser473 were detected by phosphorylated Akt signal pathway kit. Results the hippocampal neurons were extracted from the mice fed for 6 weeks. The results of flow cytometry showed that aripiprazole could significantly reduce the apoptosis rate of hippocampal neurons in CPZ model mice. Compared with the control group, the survival rate of hippocampal neurons in CPZ model mice treated with aripiprazole was significantly increased by Western blot analysis of autophagy associated protein Beclin1. The expression of Beclin1 in spinal cord of CPZ model mice was significantly increased after administration of aripiprazole, and the expression of Beclin1 was significantly decreased after administration of aripiprazole. The expression levels of total Akt and Ser473 in CPZ group were significantly lower than those in the control group (P 0.01). After taking aripiprazole, the expression level of total Akt and Ser473 increased, but there was no significant difference compared with the control group (P 0.05). Conclusion aripiprazole can protect hippocampal neurons from apoptosis through Akt signaling pathway.
【作者單位】: 武漢市精神衛(wèi)生中心醫(yī)務處;武漢市中醫(yī)醫(yī)院院辦;武漢市精神衛(wèi)生中心司法鑒定科;武漢市精神衛(wèi)生中心綜合科;
【基金】:湖南省自然科學基金(No.2015JJ1010)
【分類號】:R749.4
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本文編號:1801944
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