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艾灸“一源三歧”不同经脉穴位对大鼠下丘脑Kiss1/GPR54/GnRH神经通路影响的比较研究

批准号:
82104740
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:
王迪
依托单位:
学科分类:
腧穴与经络
结题年份:
2024
批准年份:
2021
项目状态:
已结题
项目参与者:
王迪

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中文摘要
基于“一源三歧”理论,任督冲脉同起于胞中,与胞宫生理病理密切相关,而三脉穴位临床治疗胞宫病证的取穴偏向和疗效有差异,其机制未明。前期研究发现艾灸任脉神阙、关元穴可调节妇科寒凝血瘀证模型大鼠FSH、LH、P、E2、GnRH和下丘脑β-EP、5-HT含量,改善HPG轴失调,提高卵巢功能。针灸作用途径是神经-内分泌调节,有研究表明Kisspeptin/GPR54系统是调节生殖活动中起关键作用的神经元网络之一,是HPG轴的始动因素。由此推测艾灸可能通过刺激体表穴位,刺激信号传入中枢,干预下丘脑Kiss1/GPR54系统释放GnRH,调控HPG轴而产生效应。本研究艾灸妇科寒凝血瘀证模型大鼠下腹部任脉、冲脉和腰部督脉穴位,通过比较Kiss1/GPR54/GnRH通路的响应及其对HPG轴的调控,明确“一源三歧”不同经脉穴位治疗胞宫病证的神经-内分泌机制,揭示“一源三歧”科学内涵,为临床选穴提供客观依据。
英文摘要
Based on the theory of "one source and three branches", the meridian of Ren, Du and Chong originate from the uterus, and they closely related to the physiology and pathology of uterus. However, there are differences in acupoint selection bias and clinical efficacy between the three meridians in the treatment of uterine disease, and the mechanism is not clear. Our previous research have found that Moxibustion at Shenque and Guanyuan points of Ren meridian can regulate FSH, LH, P, E2, GnRH and hypothalamic β-EP, 5-HT contents, improve HPG axis imbalance and ovarian function in rats with gynecological cold coagulation blood stasis syndrome(CCBS). The mechanism of acupuncture is neuroendocrine regulation, some studies have shown that kisspeptin / GPR54 system is one of the neural networks that play a key role in the regulation of reproductive activity, and it is the initiating factor of HPG axis. Therefore, it is speculated that moxibustion can stimulate the acupoints on the body surface, and the signal can be transmitted to the central nervous system, which may have an effect by intervening in the release of GnRH from the hypothalamic Kiss1/GPR54 system and regulating the HPG axis. In this study, moxibustion was used to intervene the Ren, Chong and Du acupoints in the lower abdomen and waist in gynecological CCBS model rats, by comparing the response of Kiss1/GPR54/GnRH central nervous pathway and its regulation on HPG axis, to clarify the neuroendocrine mechanism of different meridians and acupoints of "one source and three branches" in the treatment of uterine diseases,and to reveal the scientific connotation of "one source and three branches" and provide objective basis for clinical acupoint selection.
基于“一源三歧”理论,任督冲脉同起于胞中,与胞宫生理病理密切相关,而三脉穴位临床治疗胞宫病证的取穴偏向和疗效有差异,其机制未明。前期研究发现,艾灸任脉神阙、关元穴可调节妇科寒凝血瘀证模型大鼠生殖激素和下丘脑神经递质含量,提高卵巢功能。针灸作用途径是神经-内分泌调节,有研究表明,Kisspeptin/GPR54系统是调节生殖活动中起关键作用的神经元网络之一,是HPG轴的始动因素。本研究通过建立妇科寒凝血瘀证动物模型,采用“一源三歧”经脉穴位进行干预,比较其对妇科寒凝血瘀证模型大鼠的干预作用;采用GnRH激动剂和抑制剂进行干预,检测HPG轴效应因子,探讨“一源三歧”不同经脉穴位对HPG轴功能的影响;通过采用化学遗传技术干预Kiss1神经元,探讨艾灸“一源三歧”不同经脉穴位对Kiss1/GPR154/GnRH通路的影响。实验结果显示,艾灸后,CCBS症状评分明显降低,子宫肌电值降低,卵巢卵泡增多,子宫内膜增厚、腺体增多,子宫微循环障碍减轻,血管活性物质平衡;血清生殖激素及6-keto-PGF1α、β-EP含量上升,TXB2、5-HT、SP下降;ER、FSHR、LHR mRNA和蛋白表达上升,且“一源三歧”经脉穴位干预妇科寒凝血瘀证以任脉穴位“气海”“关元”“中级”疗效最佳。采用GnRH激动剂对照,艾灸干预后,血清HPG 轴相关的生殖激素含量升高,神经递质中疼痛效应因子含量下降;卵巢GnRHR、FSHR、LHR 及子宫ERmRNA和蛋白表达升高。采用化学遗传法抑制下丘脑kiss1神经元后,艾灸可上调下丘脑和卵巢组织中Kiss1/GPR54/GnRH 通路关键因子Kiss1、GPR54、GnRH mRNA和蛋白的表达。通过揭示“一源三歧”不同经脉穴位与胞宫相关的生物学基础,为临床选穴提供实验依据。明确HPG轴的调节作用参与经穴与胞宫相关内在机制的中心环节,进一步研究艾灸对Kiss1/GPR154/GnRH 中枢神经传导通路通路的影响,揭示该通路参与艾灸“一源三歧”不同经脉穴位治疗胞宫病证的神经-内分泌机制。
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