文章摘要
刘淑梅,李丽华,鲁俊华,高玲娟,郎玉玲.PI3k/Akt信号通路在维生素D促进神经递质分泌中的作用[J].南京医科大学学报,2020,(11):1597~1602
PI3k/Akt信号通路在维生素D促进神经递质分泌中的作用
Mechanism of vitamin D promoting the secretion of neurotransmitters via PI3k/Akt signaling pathway
投稿时间:2020-05-21  
DOI:10.7655/NYDXBNS20201105
中文关键词: 产后抑郁  维生素D  PI3k/Akt信号通路  5⁃羟色胺  去甲肾上腺素
英文关键词: postpartum depression  vitamin D  PI3k/Akt signaling pathway  5⁃hydroxytryptamine  norepinephrine
基金项目:国家自然科学基金面上项目(81571437);黑龙江省高等教育教学改革重点委托项目(SJGZ20190065 );牡丹江医学院教育教学改革重点项目(MYZD20170001)
作者单位
刘淑梅 牡丹江医学院护理学院黑龙江 牡丹江 157000 
李丽华 牡丹江医学院护理学院黑龙江 牡丹江 157000 
鲁俊华 牡丹江医学院护理学院黑龙江 牡丹江 157000 
高玲娟 南京医科大学转化医学研究院江苏 南京 210004 
郎玉玲 牡丹江医学院护理学院黑龙江 牡丹江 157000 
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中文摘要:
      目的:探讨维生素D(vitamin D,VD)调节海马神经元细胞促进神经递质分泌的可能机制。方法:采用化学发光法及酶联免疫吸附试验(ELISA)对62例产后抑郁(postpartum depression,PPD)患者以及31例健康产妇分别进行血清25羟基维生素D[25(OH)D]、5?羟色胺(5?hydroxytryptamine,5?HT)以及去甲肾上腺素(norepinephrine,NE)水平检测;对体外培养的海马神经元细胞施加不同作用因素,采用甲基噻唑基四唑(methylthiazolyltetrazolium,MTT)比色法检测海马神经元细胞的增殖率;免疫印迹法检测总Akt(total Akt,T?Akt)及磷酸化Akt(phosphorylated Akt,p?Akt)蛋白的表达情况。结果:轻度抑郁组患者的血清25(OH)D、5?HT和NE水平低于健康对照组(均P < 0.05);而重度抑郁组患者的血清25(OH)D、5?HT和NE水平与轻度抑郁组(均P < 0.05)。体外实验结果显示,VD能以剂量依赖性方式调节海马神经元细胞增殖率及5?HT、NE的分泌水平;与对照组比较,VD+阴性小干扰RNA(negative siRNA)组神经元细胞增殖率及5?HT、NE分泌水平增高(均P < 0.05);而与对照组比较,VD+VD受体小干扰RNA(VDR siRNA)组神经元细胞增殖率及5?HT、NE分泌水平差异无统计学意义(均P > 0.05);免疫印迹结果显示,与对照组比较,p?Akt蛋白的表达在VD + negative siRNA组显著增加(P < 0.01);而VD+VDR siRNA组与对照组比较,p?Akt蛋白表达无显著变化(均P > 0.05);与对照组比较,VD + DMSO组神经元细胞增殖率及5?HT、NE分泌水平显著增加(均P < 0.05);而VD + LY294002(PI3k/Akt信号通路抑制剂)组神经元细胞增殖率及5?HT、NE分泌水平,与对照组比较差异无统计学意义(均P > 0.05)。结论:VD促进海马神经元细胞活性及促进5?HT和NE的分泌,可能与PI3?k/Akt信号通路的激活有关,此作用可能在PPD的临床防治及产后护理中具有应用价值。
英文摘要:
      Objective:This study aims to investigate the possible mechanism by which vitamin D(VD) regulates the secretion of neurotransmitters in hippocampal neurons. Methods:The serum levels of 25 hydroxyvitamin D[25(OH)D],5?hydroxytryptamine(5?HT)and norepinephrine(NE)were detected by chemiluminescence and enzyme immunoassay (ELISA) in 62 postpartum depression(PPD)patients and 31 healthy pregnant women. The proliferation of hippocampal neurons was determined by methylthiazolyltetrazolium(MTT)colorimetric method. Western blotting was used to detect the expression of total Akt(T?Akt)and phosphorylated Akt(p?Akt). Results:The serum levels of 25(OH)D,5?HT and NE in the mild depressed group were lower than those in the healthy control group,and the differences were statistically significant(all P < 0.05). The serum levels of 25(OH)D,5?HT and NE in the severe depression group were significantly lower than those in the mild depression group(all P < 0.05). VD had a significant dose?dependent effect on the proliferation of hippocampal neurons and the levels of secreted 5?HT and NE in vitro. In addition,the proliferation and secreted 5?HT and NE levels of neurons were significantly different between VD+negative small interfering RNA(siRNA)group and control group(all P < 0.05). In the VD+VD receptor(VDR)siRNA group,there was no statistically significant difference in proliferation of neurons and the levels of 5?HT and NE when compared with contrd group(all P > 0.05). Western blot results showed that the expression of phosphorylated Akt in the VD+negative siRNA group was significantly increased when compared with control group,with statistical differences(P < 0.01). There was no significant difference in the expression of phosphorylated Akt between the VD+VDR siRNA group and control group(all P > 0.05). In the VD+DMSO group,the proliferation of neurons and the levels of 5?HT and NE were significantly different when compared with control group(all P < 0.05). However,there was no significant difference in proliferation of neurons and the levels of 5?HT and NE between VD+LY294002(inhibitor of PI3k/Akt signaling pathway) group and control group(all P > 0.05). Conclusion:VD promotes the activity of hippocampal neurons and secretion of 5?HT and NE,which may be related to the activation of PI3k/Akt signaling pathway. That plays an important role in the clinical prevention and treatment of PPD and postpartum care.
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