束缚应激大鼠中枢AMPA受体及相关蛋白变化与肝主疏泄的关系
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摘要
应激是机体在受到各种强烈因素(即应激原)剌激时,体内出现以交感神经兴奋和垂体-肾上腺皮质分泌增多为主的一系列神经内分泌反应,它对生物的存活具有十分重要的意义。适宜的应激反应有助于提高个体对环境的适应能力;过度的尤其是慢性应激会导致不同程度的生理、心理障碍,甚至引起躯体疾病。由于慢性应激是许多疾病发生和发展的重要因素,又与亚健康状态直接相关,上个世纪80年代以来,国内外学者对其进行了大量的研究。应激涉及了人体的多个系统,在不同应激原、不同个体、不同的环境下,可能导致的结果也不同,这给预防和治疗应激性疾病造成了困难,而中医药的整体调整、辨证论治、个体化诊疗等理念在这方面已显示出了更大的优越性。本课题为国家自然科学基金资助课题(310000216),从应激反应的中枢机制与肝主疏泄功能调节两个方面及其相互关系进行了理论探讨和实验研究。
一、理论研究
肝主疏泄是肝脏的核心生理功能,疏泄功能失常致病范围广泛,疏泄不利、气机失调是其基本病理机制。结合信息控制系统理论,通过对文献的回顾分析,认为肝主疏泄的生理学基础如下:(1)边缘系统是肝主疏泄的调控中枢,是动机和情绪产生的发源地,它一方面接受内外环境的刺激,及时做出反应;另一方面接受体内状态的反馈信息,调整其状态,产生适应性反应。(2)边缘系统的信息传递主要通过边缘系统-脑干-自主神经通路和交感-肾上腺髓质通路来实现,其中自主神经通路又分为交感神经通路和副交感神经通路。(3)平滑肌系统是肝主疏泄的效应器,通过平滑肌的舒张和收缩活动,最终完成在边缘系统控制下的整个疏泄过程。(4)糖皮质激素通过对边缘系统兴奋性和敏感性的影响,调节着肝主疏泄功能的状态和强弱。
应激反应涉及了五脏,但以心肝肾三脏最为重要。在应激过程中,心负责感觉和知觉的形成,并通过认知评价形成决策,传至皮层下中枢;处理内脏和躯体反馈信息;接受肾上腺皮质激素的调节。肝负责心下传的决策指令,在边缘系统形成情绪,并影响蓝斑-去甲肾上腺素神经元/交感-肾上腺髓质系统,引起平滑肌的收缩、血液的重新分布,完成应激心理上、生理上的反应,同时亦影响下丘脑-垂体-肾上腺皮质轴使肾上腺皮质激素分泌增多,是应激反应形成的核心。肾主要通过肾上腺皮质激素完成应激的适应性反应,并调节着心、肝对其调节的敏感性。肝肾均藏相火,在应激反应中常互相影响。
中医学认为气机的变化是机体在应激反应中所出现的重要的生理和病理反应,并导致一系列其他的生理或病理改变,而肝为气血调节之枢,肝脏功能的正常与否,直接关系到机体其他脏器的生理功能以及疾病的发生、发展和转归。因此我们课题组首先提出“应激从中医脏象理论分析,当责之于肝”的论断,认为肝是人体应激机制的调节中心,肝脏对气机、血液和情志等的影响调节人体的应激反应。另一方面,应激反应强度和时程不同,所反映的证候也不同。从文献回顾看,对应激损害的中医治法主要为疏肝、补肾、健脾、补气、调心等,结合应激反应的三个阶段的临床表现,认为在应激反应初期的临床表现类似于中医肝郁气滞证候。进入抵抗期后,在肝郁气滞的基础上又发生了各种变证如脾虚,痰结、血瘀等,随着应激原的持续存在和消耗的逐渐积累,可由实转虚、
Stress is a series of neuroendocrine responses which is marked with sympathetic nerves excitement and increase of pituitary -adrenal gland cortex secretion when organisms is expose to various factors (stress factor) stimulation. It has great significance for biological survival. Appropriate stress response is benefit to individual improvement in adaptability to environment changes, but excessive, especially chronic stress, causes physical, psychological disorders in vary degrees, and even causes body diseases. Since chronic stress is an important factor in many diseases course, and directly related to the state of sub-health, there are a large number of researchers studying on it since 1980s. Several systems involves in stress response, different stressor, different individuals and different circumstances might lead to different results, this is difficult for the prevention and treatment of stress diseases, and Chinese medicine, as a mathod of whole adjustment, treatment based on different syndromes and individualized diagnosis, has shown greater superiority. This project was supported by National Science Foundation Committee of China(310000216), and we focus on the theoretical study and experimental study on the central neural system mechanisms of stress response and the role of regulation function of liver governs smoothing qi flow(LGSQF) in stress response, the result as the following:
1 Theoretical Study
LGSQF is the core of liver physiological functions, which disorder lead to diseases in vary range, and stagnancy of liver-qi, disorder of qi activity are the basic pathological mechanism. Base on information control system theory and analysis retrospectively, we suggest the foundation physiology of LGSQF as follows : Instinctive demand of the body is the core of the liver governs smoothing qi flow; Limbic system, the center of motivation and emotion, is the regulation and control center of LGSQF; Hypothalamic- brain stem- autonomic nerve pathway and sympathetico-adrenomedullary system pathway are information pathways; Smooth muscle system is the effective appararus of LGSQF, which realizes the changes of distribution of qi, blood and body fluids by relaxation and constriction of smooth muscle to carry out liver’s function, and transmit this changes to limbic system for feedback regulation through sensory nerve system; And the adrenal cortical hormone play a role in maintaining a normal level and changes.
Five zang-organs are involved in stress response, but heart, liver and kidney in them are the most important. In the course of stress response, the heart is in charge of the formation of sensation and perception, makes decision after cognitive appraisal, and then transmits the decision to subcortical center; it processes the feedback of the internal organs and the body; and it also is regulated by adrenal cortical hormone. Liver, that receives the decision from heart, forms emotion in limbic system and acts on locus coeruleus- norepinephrine/
一、理论研究
肝主疏泄是肝脏的核心生理功能,疏泄功能失常致病范围广泛,疏泄不利、气机失调是其基本病理机制。结合信息控制系统理论,通过对文献的回顾分析,认为肝主疏泄的生理学基础如下:(1)边缘系统是肝主疏泄的调控中枢,是动机和情绪产生的发源地,它一方面接受内外环境的刺激,及时做出反应;另一方面接受体内状态的反馈信息,调整其状态,产生适应性反应。(2)边缘系统的信息传递主要通过边缘系统-脑干-自主神经通路和交感-肾上腺髓质通路来实现,其中自主神经通路又分为交感神经通路和副交感神经通路。(3)平滑肌系统是肝主疏泄的效应器,通过平滑肌的舒张和收缩活动,最终完成在边缘系统控制下的整个疏泄过程。(4)糖皮质激素通过对边缘系统兴奋性和敏感性的影响,调节着肝主疏泄功能的状态和强弱。
应激反应涉及了五脏,但以心肝肾三脏最为重要。在应激过程中,心负责感觉和知觉的形成,并通过认知评价形成决策,传至皮层下中枢;处理内脏和躯体反馈信息;接受肾上腺皮质激素的调节。肝负责心下传的决策指令,在边缘系统形成情绪,并影响蓝斑-去甲肾上腺素神经元/交感-肾上腺髓质系统,引起平滑肌的收缩、血液的重新分布,完成应激心理上、生理上的反应,同时亦影响下丘脑-垂体-肾上腺皮质轴使肾上腺皮质激素分泌增多,是应激反应形成的核心。肾主要通过肾上腺皮质激素完成应激的适应性反应,并调节着心、肝对其调节的敏感性。肝肾均藏相火,在应激反应中常互相影响。
中医学认为气机的变化是机体在应激反应中所出现的重要的生理和病理反应,并导致一系列其他的生理或病理改变,而肝为气血调节之枢,肝脏功能的正常与否,直接关系到机体其他脏器的生理功能以及疾病的发生、发展和转归。因此我们课题组首先提出“应激从中医脏象理论分析,当责之于肝”的论断,认为肝是人体应激机制的调节中心,肝脏对气机、血液和情志等的影响调节人体的应激反应。另一方面,应激反应强度和时程不同,所反映的证候也不同。从文献回顾看,对应激损害的中医治法主要为疏肝、补肾、健脾、补气、调心等,结合应激反应的三个阶段的临床表现,认为在应激反应初期的临床表现类似于中医肝郁气滞证候。进入抵抗期后,在肝郁气滞的基础上又发生了各种变证如脾虚,痰结、血瘀等,随着应激原的持续存在和消耗的逐渐积累,可由实转虚、
Stress is a series of neuroendocrine responses which is marked with sympathetic nerves excitement and increase of pituitary -adrenal gland cortex secretion when organisms is expose to various factors (stress factor) stimulation. It has great significance for biological survival. Appropriate stress response is benefit to individual improvement in adaptability to environment changes, but excessive, especially chronic stress, causes physical, psychological disorders in vary degrees, and even causes body diseases. Since chronic stress is an important factor in many diseases course, and directly related to the state of sub-health, there are a large number of researchers studying on it since 1980s. Several systems involves in stress response, different stressor, different individuals and different circumstances might lead to different results, this is difficult for the prevention and treatment of stress diseases, and Chinese medicine, as a mathod of whole adjustment, treatment based on different syndromes and individualized diagnosis, has shown greater superiority. This project was supported by National Science Foundation Committee of China(310000216), and we focus on the theoretical study and experimental study on the central neural system mechanisms of stress response and the role of regulation function of liver governs smoothing qi flow(LGSQF) in stress response, the result as the following:
1 Theoretical Study
LGSQF is the core of liver physiological functions, which disorder lead to diseases in vary range, and stagnancy of liver-qi, disorder of qi activity are the basic pathological mechanism. Base on information control system theory and analysis retrospectively, we suggest the foundation physiology of LGSQF as follows : Instinctive demand of the body is the core of the liver governs smoothing qi flow; Limbic system, the center of motivation and emotion, is the regulation and control center of LGSQF; Hypothalamic- brain stem- autonomic nerve pathway and sympathetico-adrenomedullary system pathway are information pathways; Smooth muscle system is the effective appararus of LGSQF, which realizes the changes of distribution of qi, blood and body fluids by relaxation and constriction of smooth muscle to carry out liver’s function, and transmit this changes to limbic system for feedback regulation through sensory nerve system; And the adrenal cortical hormone play a role in maintaining a normal level and changes.
Five zang-organs are involved in stress response, but heart, liver and kidney in them are the most important. In the course of stress response, the heart is in charge of the formation of sensation and perception, makes decision after cognitive appraisal, and then transmits the decision to subcortical center; it processes the feedback of the internal organs and the body; and it also is regulated by adrenal cortical hormone. Liver, that receives the decision from heart, forms emotion in limbic system and acts on locus coeruleus- norepinephrine/
引文
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