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补肾活血通过激活脑源性神经营养因子介导的信号通路改善血管性痴呆大鼠的认知功能。

Bushenhuoxue improves cognitive function and activates brain-derived neurotrophic factor-mediated signaling in a rat model of vascular dementia.

机构信息

General Medical Practice, Shuangyushu Community Health Service Center of Haidian District, Beijing 100086, China.

Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, China.

出版信息

J Tradit Chin Med. 2020 Feb;40(1):49-58.

Abstract

OBJECTIVE

To explore the protective mechanisms of the Traditional Chinese Medicine Bushenhuoxue (BSHX) in a rat model of vascular dementia (VD).

METHODS

A rat model of VD was developed using bilateral common carotid artery occlusion (BCCAO). Rats were administered BSHX (10.14 or 5.07 g/kg), nimodipine (11.06 mg/kg; positive control), or saline (control) by gavage daily for 30 d post-surgery. Learning and memory abilities were assessed using the Morris water maze. Morphological changes in the hippocampus were observed using light microscopy (hematoxylin and eosin staining) and transmission electron microscopy (TEM). The mRNA and protein expression levels of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), phosphatidyl inositol 3-kinase (PI3K), serine/threonine kinase (AKT), and cAMP response element binding protein (CREB) were measured by real-time polymerase chain reaction (RT-PCR) and Western blot, respectively.

RESULTS

Compared with the sham group, rats with BCCAO exhibited impaired learning and memory abilities (Morris water maze) and showed abnormalities in neuronal morphology (light microscopy) and ultrastructure (TEM) in the hippocampus. They also had decreased mRNA and protein expressions of BDNF, TrkB, PI3K, AKT, and CREB in hippocampal tissue (all P < 0.05). In rats with BCCAO, administration of BSHX attenuated deficits in learning and memory, improved the morphology and ultrastructure of hippocampal neurons, and enhanced mRNA and protein expression levels of BDNF, TrkB, PI3K, AKT, and CREB (all P < 0.05).

CONCLUSION

BSHX may protect hippocampal neurons and improve learning and memory abilities, at least in part via the activation of BDNF/TrkB/PI3K/AKT/CREB signaling.

摘要

目的

探讨补肾活血方(BSHX)在血管性痴呆(VD)大鼠模型中的保护机制。

方法

采用双侧颈总动脉结扎(BCCAO)建立 VD 大鼠模型。术后每日通过灌胃给予 BSHX(10.14 或 5.07 g/kg)、尼莫地平(阳性对照,11.06 mg/kg)或生理盐水(对照),共 30 天。使用 Morris 水迷宫评估学习和记忆能力。使用光镜(苏木精和伊红染色)和透射电镜(TEM)观察海马的形态变化。通过实时聚合酶链反应(RT-PCR)和 Western blot 分别测量脑源性神经营养因子(BDNF)、酪氨酸受体激酶 B(TrkB)、磷酸肌醇 3-激酶(PI3K)、丝氨酸/苏氨酸激酶(AKT)和 cAMP 反应元件结合蛋白(CREB)的 mRNA 和蛋白表达水平。

结果

与假手术组相比,BCCAO 大鼠表现出学习和记忆能力受损(Morris 水迷宫),并显示出海马神经元形态(光镜)和超微结构(TEM)异常。它们的海马组织中 BDNF、TrkB、PI3K、AKT 和 CREB 的 mRNA 和蛋白表达也降低(均 P<0.05)。在 BCCAO 大鼠中,BSHX 给药可减轻学习和记忆缺陷,改善海马神经元的形态和超微结构,并增强 BDNF、TrkB、PI3K、AKT 和 CREB 的 mRNA 和蛋白表达水平(均 P<0.05)。

结论

BSHX 可能通过激活 BDNF/TrkB/PI3K/AKT/CREB 信号通路来保护海马神经元并改善学习和记忆能力。

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