CHEMICAL, MORPHOLOGICAL & FUNCTIONAL STUDY OF MERIDIANS

描述：(改编自申请人的摘要)-经络系统是 针灸的中心理论，并作为指导原则 许多替代疗法的诊断和治疗。调查人员已经 在人和动物身上都证明了穴位/经络具有 具有低阻的特点。首席调查员已经 新近发现神经元型一氧化氮合酶(NNOS)蛋白水平和 三经皮肤中一氧化氮(NO)含量持续升高 包含大鼠皮肤低阻点(LSRP)的区域。校长 研究人员的组织化学检查显示，nNOS的表达是 神经纤维、轴突、神经元和毛囊显著增加。 经络/穴位。与NO的假定作用一致，LSRP是 表现在大鼠和正常小鼠身上。相反，在nNOS基因敲除小鼠中， 阻力增加了。此外，初步数据显示，外源NO 减少LSRP中的阻力，同时通过封锁减弱响应 去甲肾上腺素能功能。首席调查员假设1)不 是一种重要的经络化学物质，皮肤中nNOS表达增强是一种 经络/穴位结构的组织化学标志；2)NO升高去甲肾上腺素 释放局部促进交感神经功能并调节 穴位/经络的生物物理特征。鉴于关键的 经络系统的重要性和未开发的领域，主要目标是 这一建议是：1)穴位中nNOS-NO水平是否选择性增加 和/或在经络区域？2)L精氨酸衍生的没有合成和 针灸改变穴位/经络中NO的释放？3)什么是 NNOS在LSRP和经络中的表达分布 一氧化氮合酶在LSRP中的表达及皮肤阻力的消除/降低 基因敲除老鼠？5)L精氨酸衍生的NO合成是否增加脑组织的周转？ 穴位/经络生物物理特性的调节因子？这个 拟议的研究将检查nNOS表达的定位，结合 检测LSRP/经络前后皮肤组织的结构分析 通过电学方法。神经元型一氧化氮合酶蛋白、mRNA、NE、NO的定量 代谢物将与神经药物操作和 LSRP的电生理学检查以验证大鼠的假说， 转基因小鼠和人类。这一结果应该会推动 了解nNOS-NO在神经化学、形态和免疫反应中的作用 为经络/穴位的功能基础，并产生关于 一氧化氮对去甲肾上腺素能激活介导生物物理的影响 穴位/经络的特点。

DESCRIPTION: (Adapted from the applicant's abstract) - The meridian system is the central theory of acupuncture, and serves as a guiding principle for diagnosis and treatment of many alternative therapies. Investigators have demonstrated in both humans and animals that acupoints/meridians possess characteristics of low electric resistance. The principal investigator has recently found that neuronal nitric oxide synthase (nNOS) protein levels and nitric oxide (NO) content are consistently increased in the three meridian skin regions containing low skin resistance points (LSRP) in rats. The principal investigator's histochemical examinations reveal that nNOS expression is markedly increased in nerve fibers, axons, neurons, and hair follicles in the meridians/acupoints. Consistent with the postulated role of NO, LSRP are manifested in rats and normal mice. In contrast, in nNOS knockout mice the resistance is increased. Furthermore, preliminary data show that exogenous NO reduces the resistance in LSRP while the responses are attenuated by blockade of noradrenergic function. The principal investigator hypothesizes that 1) NO is an important meridian chemical and enhanced nNOS expression in the skin is a histochemical marker of meridian/acupoint structures, and 2) NO increases NE release which locally facilitates sympathetic function and mediates the biophysical characteristics of acupoints/meridians. In view of the critical importance and unexplored territory of the meridian system, the major goals of this proposal are: 1) Are nNOS-NO levels selectively increased in the acupoints and/or in the meridian regions? 2) Does L-arginine-derived NO synthesis and acupuncture modify NO release in acupoints/meridians? 3) What are the distributions of nNOS expression in the LSRP and meridian lines? 4) Are nNOS expressions and the skin resistance abolished/reduced in the LSRP of nNOS knockout mice? And 5) does L-arginine-derived NO synthesis increase turnover of NE that mediates biophysical characteristics of acupoints/meridians? The proposed studies will examine localization of nNOS expression, combined with structural analysis of the skin tissues with or without LSRP/meridians detected by electrical methods. Quantification of nNOS protein, mRNA, NE, and NO metabolites will be integrated with neuropharmacological manipulations and electrophysiological examination of LSRP to test the hypotheses in rats, genetically-altered mice, and humans. The results should advance the understanding of the roles of nNOS-NO on a neurochemical, morphological, and functional basis for meridians/acupoints, and yield new insights regarding the effects of NO on noradrenergic activation that mediates the biophysical characteristics of acupoints/meridians.