酸枣仁汤调节PI3K/AKT/BDNF信号通路改善围绝经期大鼠失眠作用机制OACSTPCD
Action mechanism of Suanzaoren decoction regulates PI3K/AKT/BDNF signaling pathway to improve insomnia in perimenopausal rats
目的:探讨酸枣仁汤调节磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)/脑源性神经生长因子(BDNF)信号通路对围绝经期失眠大鼠的改善作用.方法:通过摘除卵巢建立围绝经期失眠大鼠模型,并将大鼠随机分为失眠组、不同剂量(3.25、7.50、15 g/kg)酸枣仁汤组、抑制剂LY294002[2 ng/(ml·kg)]联合15 g/kg酸枣仁汤组,并以切除卵巢周围脂肪组织的大鼠为假手术组.观察大鼠一般状况,评估大鼠睡眠质量;ELISA检测各组血清中促卵泡素(FSH)、雌二醇(E2)水平;免疫组化检测脑组织中5-羟色胺(5-HT)表达;qRT-PCR及Western blot检测PI3K/AKT/BDNF通路相关基因及蛋白表达.结果:与假手术组相比,失眠组大鼠睡眠潜伏期、E2、脑组织5-HT表达、PI3K mRNA、AKT mRNA、BDNF mRNA表达及相应蛋白显著降低,睡眠持续期、FSH显著增加(P＜0.05).与失眠组相比,不同剂量的酸枣仁汤干预后,大鼠睡眠潜伏期、E2、脑组织5-HT表达、PI3K mRNA、AKT mRNA、BDNF mRNA表达及相应蛋白显著增加,睡眠持续期、FSH显著降低,以15 g/kg酸枣仁汤干预效果最好(P＜0.05).与15 g/kg酸枣仁汤组相比,联合组大鼠睡眠潜伏期、E2、脑组织5-HT表达、PI3K mRNA、AKT mRNA、BDNF mRNA表达及相应蛋白显著降低,睡眠持续期、FSH显著增加(P＜0.05).结论:酸枣仁汤通过调节PI3K/AKT/BDNF信号通路能够有效改善围绝经期失眠大鼠症状.
Objective:To explore improvement effect of Suanzaoren decoction on perimenopausal insomnia rats by regulating phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)/brain derived neurotrophic factor(BD-NF)signaling pathway.Methods:Perimenopausal insomnia rat model were established by removing ovaries.The rats were randomly divided into insomnia group,different doses(3.25,7.50,15 g/kg)of Suanzoren decoction group,in-hibitor[2 ng/(ml·kg)]combined with 15 g/kg Suanzoren decoction group,and rats with peri-ovarian adipocytes ex-cised were used as sham operation group.The rats with adipose tissue around ovaries were used as the sham surgery group.General condition of rats were observed,and sleep quality of rats evaluated.ELISA was applied to detect levels of follicle stimulating hormone(FSH)and estradiol(E2)in the serum of each group.Immunohistochemistry was ap-plied to detect expression of serotonin(5-HT)in brain tissue.qRT-PCR and Western blot were applied to detect ex-pression of genes and proteins related to the PI3K/AKT/BDNF pathway.Results:Compared with the sham surgery group,sleep latency,E2,5-HT expression in brain tissue,PI3K mRNA,AKT mRNA,BDNF mRNA expression,and corresponding protein expression were obviously reduced in the insomnia group,while sleep duration and FSH were obviously increased(P＜0.05).Compared with the insomnia group,after intervention with different doses of Suanza-oren decoction,sleep latency,E2,5-HT expression in brain tissue,PI3K mRNA,AKT mRNA,BDNF mRNA expres-sion and corresponding protein expression were obviously increased,while sleep duration and FSH were obviously de-creased,the intervention effect of 15 g/kg Suanzaoren decoction was the best(P＜0.05).Compared with the 15 g/kg Su-anzaoren decoction group,the sleep latency,E2,5-HT expression in brain tissue,PI3K mRNA,AKT mRNA,BDNF mRNA expression and corresponding protein expression were obviously reduced in the combination group,while sleep duration and FSH were obviously increased(P＜0.05).Conclusion:Suanzaoren decoction can effectively im-prove symptoms of insomnia in perimenopausal rats by regulating PI3K/AKT/BDNF signaling pathway.
邓元香;彭雄;贺婷
湖南中医药大学第一附属医院,湖南长沙 410009
中医学
失眠酸枣仁汤脑源性神经生长因子磷脂酰肌醇3激酶围绝经期
InsomniaSuanzaoren decoctionBrain derived neurotrophic factorPhosphatidyl inositol 3 kinasePeri-menopause
《陕西中医》 2024 (007)
897-901 / 5
湖南省优秀青年科学基金资助项目(2020JJ4469)
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