围绝经期非器质性失眠妇女肝郁与PI3K/Akt信号通路的相关性研究

The interrelationship of liver depression and PI3K/Akt signaling pathway of perimenopause women with non-organic onsomnia

关键词:  围绝经期  非器质性失眠  肝郁  PI3K/Akt

Key words:  perimenopause  non-organic insomnia  liver depression  PI3K/Akt

摘要:

[目的]探讨肝郁影响围绝经期非器质性失眠的可能免疫学机制。[方法]收集围绝经期非器质性失眠妇女150例，通过四诊信息的采集获得患者的肝郁证素积分、肝郁分级及匹兹堡睡眠质量指数（PSQI），运用蛋白免疫印迹法（Western Blot）检测外周血单个核细胞（PBMC）中磷脂酰肌醇3激酶（PI3K）、蛋白激酶B（Akt）和磷酸化蛋白激酶B（pAkt）的蛋白表达量，实时荧光定量PCR法（RT-QPCR）检测PBMC中PI3K、Akt的mRNA含量，酶联免疫吸附法（ELISA）检测白介素1-β（IL-1β）、肿瘤坏死因子-α（TNF-α）水平。观察围绝经期非器质性失眠妇女的肝郁分级、PI3K/Akt信号通路各指标（PI3K、Akt、pAkt的蛋白表达量，PI3K mRNA、Akt mRNA含量；IL-1β、TNF-α水平）和PSQI之间的相互关系。[结果]1）围绝经期非器质性失眠妇女中，肝郁分级与PSQI、PI3K/Akt信号通路各指标均呈正相关（P<0.01）；IL-1β、TNF-α均与PSQI呈正相关（P<0.01）；PI3K、Akt与其相应的基因水平分别呈正相关（P<0.01）。2）PSQI、PI3K/Akt信号通路各指标在不同肝郁分级间的差异均具有统计学意义（P<0.01），且肝郁分级越高，PSQI和PI3K/Akt信号通路各指标含量越高。[结论]肝郁是诱发或加重围绝经期非器质性失眠的病因之一。是通过影响PI3K/Akt信号通路，促使PBMC中PI3K mRNA和Akt mRNA含量增加，经基因表达后使PI3K、Akt和pAkt蛋白含量上升，经一系列级联反应后，进一步提高血清中IL-1β与TNF-α的含量，最终影响围绝经期妇女非器质性失眠。故今后研究可考虑通过阻断PI3K/Akt信号通路以改善围绝经期妇女非器质性失眠。

Abstract:

[Objective] In order to understand the relationship between the liver depression and non-organic insomnia,interpretate the part of immunological mechanism of liver depression affecting non-organic insomnia of perimenopausal women.[Methods] One hundred fifty cases of perimenopausal women were collected four diagnostic information,Pittsburgh Sleep Quality Index information(PSQI) and integral and grade of liver depression. And we detected sex hormone levels in serum(including FSH, LH, E2) by electro-chemistry immunity analytical method, PI3K,Akt and pAkt protein expression in PBMC by Western Blot,PI3K mRNA and Akt mRNA content in PBMC by real-time quantitative PCR assay, while the levels of IL-1β and TNF-α in serum are measured by enzyme-linked immunosorbent assay(ELISA).[Results] 1)In perimenopausal women with non-organic insomnia,the grade of liver depression has a positive correlation with PSQI, PI3K, Akt and pAkt protein expression in PBMC (P<0.01). PI3K has a positive correlation with PI3K mRNA,Akt also has a positive correlation with Akt mRNA(P<0.01). IL-1β and TNF-α have a positive correlation with PSQI(P<0.01). 2)In perimenopausal women with non-organic insomnia, PI3K,Akt and pAkt protein expression and mRNA content in PBMC among different grade of liver depression also have statistically significance(P<0.01), and the higher grade of liver depression,the higher mRNA content and protein expression.[Conclusion] Liver depression is one of the reasons that can induce or aggravate perimenopausal non-organic insomnia. Liver depression may affect PI3K/Akt signaling pathway by increasing mRNA content of PI3K and Akt,as gene expressing,the protein expression of PI3K,Akt and pAkt is increasing,too, after a cascade reaction, to improve the levels of IL-1β and TNF-α in serum,and ultimately affect sleep in perimenopausal women with non-organic insomnia. So we can consider to research by blocking PI3K/Akt signaling pathway to improve sleep quality in perimenopausal women with non-organic insomnia in the future.