NGF在运动改善原发性痛经中的作用及机制研究
批准号:
82102669
项目类别:
青年科学基金项目(C类)
资助金额:
30.0 万元
负责人:
赵影
依托单位:
学科分类:
康复治疗与康复机制
结题年份:
2024
批准年份:
2021
项目状态:
已结题
项目参与者:
赵影
中文摘要
近年来的研究报道运动在原发性痛经(Primary dysmenorrhea, PD)的治疗中发挥积极作用,但其作用机制仍不清楚。课题组前期对6770名PD患者进行了全基因组关联分析及验证,发现神经生长因子(Nerve Growth Factor, NGF)基因多态性与PD存在强阳性关联。基于此,本研究进一步把NGF与PD的疼痛信号传导关键激酶(MAPK)联系起来,首次探索PD疼痛运动干预后中枢疼痛调控机制。通过建立PD小鼠模型,观察4周不同运动强度跑台运动对PD小鼠背根神经节内NGF及其受体表达、MAPK信号通路各分子表达及磷酸化水平的影响。此外,通过各组小鼠背根神经节细胞培养,使用NGF表达刺激剂和抑制剂以及RNA干扰(RNAi)技术,观察NGF表达的变化与MAPK通路各分子之间的关系。以期通过动物研究和细胞实验的结合,阐明NGF在运动改善PD疼痛中的作用及分子机制。
英文摘要
Recent studies have reported that exercise may play an active role in the treatment of primary dysmenorrhea (PD), but its mechanism is still unclear. We conducted a genome-wide association analysis and verification on 6770 PD patients, and found that NGF gene polymorphisms were positively associated with PD. We plan to link NGF with MAPK for pain signal transduction, and explores the mechanism of central pain regulation after PD pain exercise intervention for the first time. By establishing a PD mouse model, we observed the effects of treadmill exercise with different exercise intensities for 4 weeks on the expression of NGF and its receptors in the dorsal root ganglia. The influence of the expression and phosphorylation level of each molecule in the MAPK signaling pathway. In addition, through the culture of mouse dorsal root ganglion cells in each group, using NGF expression stimulators and inhibitors, and RNA interference (RNAi) technology, the relationship between the changes in NGF expression and the molecules in the MAPK pathway was observed. It is hoped that through the combination of animal research and cell experiment, supplement the role and molecular mechanism of NGF in improving PD pain by exercise.
运动可以缓解原发性痛经(Primary Dysmenorrhea, PD)症状,但其中的分子机制尚不清楚。我们通过建立PD大鼠模型,进行不同运动强度(小强度、中等强度和大强度)的运动干预,结果证明运动可以减少PD大鼠扭体行为发生次数,降低疼痛阈值,且这种效应与运动强度存在剂量效应,即对着运动强度的增大,PD症状越轻。进一步通过分子生物学实验发现,运动通过降低被根神经节中NGF的表达,进而抑制NGF-TrkA-ERK1/2信号通路的过度激活,大强度尤为明显。通过对前额叶蛋白组学分析发现,低强度运动主要影响调节产热和抗炎(TNF信号)相关信号通路;中等强度运动则是增强突触传递(谷氨酸能突触)和神经修复(神经退行性疾病通路);大强度运动通过强化神经信号整合(多巴胺能突触、逆行内源性大麻素信号)改善PD疼痛症状。总体上,本研究从不同视角揭示运动缓解PD疼痛的机制,为临床制定个性化运动处方提供理论依据。
具核梭杆菌通过琥珀酸诱导炎性巨噬细胞极化加剧IBD中肠神经元丢失的机制研究
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批准号:82300625
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项目类别:青年科学基金项目
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资助金额:30.00万元
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批准年份:2023
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负责人:赵影
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依托单位:
国内基金
海外基金