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目的 探讨左归丸缓解脑衰老小鼠认知障碍的作用以及机制。方法 48只SPF级雌性KM小鼠随机分为正常组(Control组)，其余40只行手术并分为假手术组(Sham组)、去卵巢组(OVX组)、左归丸组(ZGW组)、左归丸+ERs核受体阻断剂ICI182780组(ZGW+ICI182780组)和雌二醇组(E2组)，每组8只。阴道涂片确认卵巢切除造模成功后，Control组给予皮下注射0.9%氯化钠注射液，其余各组行皮下注射D-半乳糖(D-gal)300 mg/(kg·d)，ZGW组、ZGW+ICI182780组小鼠每日灌胃左归丸溶液2.635 g/kg，其中ZGW+ICI182780组腹腔注射ERs核受体阻断剂ICI182780 0.075 g/kg，E2组每日灌胃戊酸雌二醇溶液0.13 mg/kg，其余3组连续等体积纯水灌胃，持续8周。通过Morris水迷宫和新物体识别实验检测小鼠学习记忆能力，用苏木精-伊红(HE)染色法观察小鼠海马CA1区的病理形态变化，酶联免疫吸附法(ELISA)法检测小鼠血清雌二醇(E2)以及海马组织炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素(IL)-6水平，蛋白免疫印迹(Western blot)法及反转录荧光定量聚合酶链反应(RT-qPCR)法检测ERα/SIRT1/NF-κB通路相关蛋白及基因表达水平。结果 与OVX组相比，ZGW组和E2组学习记忆能力明显增强(P<0.01)，HE结果显示海马CA1区神经元形态恢复，ELISA结果表明血清中E2水平显著上调，海马中TNF-α、IL-1β、IL-6含量明显降低(P<0.01)，Western blot及RT-qPCR结果显示海马中ERα、SIRT1蛋白表达及mRNA表达水平显著上调，p-p65/p65比值明显降低(P<0.01)，而ZGW+ICI182780组则可逆转上述部分指标。结论 左归丸可以改善脑老化小鼠认知障碍，其机制可能与调节ERα/SIRT1/NF-κB信号通路、缓解神经炎症密切相关。
Abstract：Objective To determine the effect and mechanism of Zuogui pill (ZGW) on alleviating cognitive impairment in brain-aging mice.Methods Forty-eight SPF female KM mice were randomly divided into a control group (Control).Another 40 mice underwent surgery and were further divided into a sham-operation group (Sham),an ovariectomized group (OVX),a ZGW group (ZGW),a ZGW + ICI182780 group (ZGW +ICI182780),and an estradiol group (E2),8 mice in each group.After confirmation of successful OVX modeling via vaginal smear,the Control group received subcutaneous injection of 0.9% sodium chloride injection.The remaining groups received subcutaneous injection of D-galactose (D-gal) at 300 mg/(kg·d).Mice in the ZGW and ZGW+ICI182780 groups received a daily oral administration of 2.635 g/kg ZGW,with mice in the ZGW+ICI182780 group additionally receiving the intraperitoneal injections of ERs nuclear receptor antagonist ICI182780 at 0.075 g/kg daily.The E2 group received a daily oral administration of estradiol valerate solution at 0.13 mg/kg,while the remaining 3 groups received continuous oral administration of an equal volume of pure water for 8 weeks.The learning and memory abilities were assessed with the Morris water maze and novel object recognition tests.Histopathological changes in the hippocampal CA1 region were examined by hematoxylin-eosin (HE) staining.Enzyme-linked immunosorbent assay (ELISA) was used to assess the serum estradiol (E2) levels and hippocampal tissue levels of inflammatory cytokines-tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β),and interleukin-6 (IL-6) levels in the hippocampal tissue.Western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to assess the expression levels of proteins and genes related to the ERα/SIRT1/NF-κB pathway.Results Compared with the OVX group,both the ZGW and E2 groups exhibited significantly enhanced learning and memory abilities (P<0.01).HE examination revealed restored neuronal morphology in the hippocampal CA1 region.ELISA indicated markedly elevated serum E2 levels,while the hippocampal TNF-α,IL-1β,and IL-6 contents was significantly reduced (P<0.01).Western blot and RT-qPCR showed obvious upregulation of ERα and SIRT1 protein expression and mRNA expression levels in the hippocampus,with a marked decrease in the p-p65/p65 ratio (P<0.01).The ZGW+ICI182780 group reversed some of the above indicators.Conclusion ZGW may improve cognitive impairment in brain-aging mice.Its mechanism may be closely related to regulating the ERα/SIRT1/NF-κB signaling pathway and alleviating neuroinflammation.
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基本信息:
中图分类号:R285.5
引用信息:
[1]胡静玉,黄杨,张梦迪,等.左归丸介导ERα/SIRT1/NF-κB通路对脑衰老小鼠认知障碍的影响[J].中南药学,2026,24(03):47-53.
基金信息:
国家自然科学基金青年科学基金项目(No.81403288);国家自然科学基金面上项目(No.82074288)
2026-03-19
2026-03-19