基于Sirt1/FoxO1通路促进血管新生探讨柴胡疏肝散“行气解郁”的神经再生机制

批准号:
82004109
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
赵静洁
依托单位:
学科分类:
中西医结合临床基础
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
赵静洁
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中文摘要
抑郁症患病率高,治愈率低,疾病负担重,其可能由血管新生受阻导致神经再生障碍引起。我们前期发现柴胡疏肝散具有促进血管新生、恢复神经再生的作用,但因中药成分入血后较难突破血脑屏障,故其是否通过促进血管新生恢复神经再生尚不清楚。网络药理学预测Sirt1/FoxO1通路是柴胡疏肝散促进血管新生发挥抗抑郁作用的重要靶点,尚未实验证实。本课题拟首先观察柴胡疏肝散干预抑郁大鼠血管新生和神经再生的作用;第二,通过阻断大鼠海马血管新生观察神经再生情况,并且以血管内皮细胞与神经干细胞共培养,探索柴胡疏肝散是否通过促进血管新生恢复神经再生功能;第三,通过阻断大鼠海马内皮细胞的Sirt1/FoxO1通路,观察血管新生情况,并用Sirt1阻断剂处理内皮细胞,观察其增殖和成管功能,揭示柴胡疏肝散是否通过Sirt1/FoxO1通路促进血管新生。为柴胡疏肝散行气(血管新生)解郁(神经再生)的科学内涵提供实验基础。
英文摘要
Major depressive disorder has a high prevalence but low treatment and the concomitant heavy economic burden of disease. Adult hippocampus neurogenesis is inhibited by vascular dysfunction may contribute to the pathophysiological basis of major depressive disorder. We have previously discovered that Chaihu Shugan Power has the effect of promoting angiogenesis and neurogenesis. Because angiogenesis is beneficial to neurogenesis, Chaihu Shugan can directly act on vascular endothelial cells after dispersing into the blood. Network pharmacological prediction of the common targets of this drug and depression demonstrates that Sirt1 / FoxO1 is particularly prominent in promoting angiogenesis. However, it is unclear whether or not the mechanism by which this pathway increases angiogenesis, and therefore, promotes neurogenesis.The objectives of this study are (1) to observe the antidepressant effect of Chaihu Shugan Powder on angiogenesis and neurogenesis in depressed rats; (2) to co-culture neural stem cells(NSCs) with Brain Microvascular endothelial cells(BMECs) that has been selectively knocked down of Sirt1 in SGZ area to block angiogenesis to explore whether Chaihu Shugan Powder promotes neurogenesis through angiogenesis; (3) to detect Sirt1/FoxO1 pathway-related proteins through Sirt1 knockdown rats and BMECs treated with Sirt1 inhibitors to explore whether Chaihu Shugan Powder exerts its mechanism of promoting angiogenesis through the vascular endothelial cell Sirt1 / FoxO1 pathway. This study will provide experimental evidence for the neurogenesis mechanism and scientific connotation of "Chaihu Shugan Powder".
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DOI:10.1016/j.jad.2021.09.064
发表时间:2021-09
期刊:Journal of affective disorders
影响因子:6.6
作者:Wei Shi;Shan Zhang;Yujia Lu;Yaning Wang;Jing-jie Zhao;Li Li-Li
通讯作者:Wei Shi;Shan Zhang;Yujia Lu;Yaning Wang;Jing-jie Zhao;Li Li-Li
DOI:10.1186/s12888-022-04065-0
发表时间:2022-06-22
期刊:BMC psychiatry
影响因子:4.4
作者:
通讯作者:
DOI:--
发表时间:2022
期刊:现代中医临床
影响因子:--
作者:徐帅;赵静洁
通讯作者:赵静洁
DOI:10.3760/cma.j.cn371468-20210918-00538
发表时间:2022
期刊:中华行为医学与脑科学杂志
影响因子:--
作者:卢宇佳;张珊;史伟;李丽;赵静洁
通讯作者:赵静洁
DOI:10.2147/dddt.s370825
发表时间:2022
期刊:Drug design, development and therapy
影响因子:--
作者:
通讯作者:
国内基金
海外基金
