基于脑功能成像技术探讨针刺太溪穴的双向调节效应机制
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摘要
背景：
针刺的双向调节作用是通过针刺经穴,使机体或靶器官由异常兴奋状态得到抑制,由异常的抑制状态得到兴奋,或其他层次上的改变,最终目的是使机体由异常的病理状态恢复到或趋向于正常的生理状态或达到一个新的平衡状态,等同于中医基础理论所强调的“阴平阳秘”状态。针刺经穴双向调节作用是针灸作用重要特点之一,但其规律与机理目前还未得到明确的解释,针刺的双向调节作用研究也是近年来针灸作用规律研究的重要方向。
针刺的双向调节效应与腧穴的穴性、腧穴的配伍、机体所处的机能状态、针刺刺激的方式及治疗时机等密切相关。其中,机体的状态是针刺双向调节作用发挥的基础。人体是一个物质、能量、信息的集合体,针刺腧穴对机体的双向调节效应依赖于腧穴自身的物质基础,通过激发调节这些物质,使我们机体对于自身状态产生反馈效应,达到物质、能量与信息的传递交流。
针刺腧穴作为一个外在刺激可能首先激活了相应的中枢神经系统,通过中枢神经系统而调控神经、内分泌、免疫网络,继而影响靶效应器官。现代医学已经积累了大量的外周器官与大脑相互联系的证据。导师赖新生教授提出了“经穴效应与脑相关”的假说。他认为人体作为一个生物体,针刺穴位干预的反应和调节作用必须经过脑作为中枢的调节和整合(即信息的传导和转导),再作用于靶效应器官,从而实现治疗效应。在此基础上,针刺经穴位的双向良性调节作用是经穴治疗效应的体现,在中枢脑层面也应该有所体现,即：经穴双向良性调节作用与脑相关。
21世纪是“脑的世纪”,脑科学是全世界科学的前沿学科。脑科学相关技术的巨大发展为揭示经穴脑效应的奥妙创造了有利的客观条件。随着脑功能成像技术的发展,尤其是功能磁共振成像(functional magnetic resonance imaging, fMRI)和正电子发射层成像(positron emission tomography, PET)等技术日益发展,针刺腧穴对脑中枢效应的研究进入了崭新的领域。与以往生化及物理技术不同的是,脑功能成像技术可以在无创状态下,动态地在活体和从整体水平上来研究针刺经穴对脑功能状态的调节效应,实现功能的可视化。脑功能成像技术中,正激活与负激活的概念反映了机体大脑功能调节状态,从正负激活角度观察针刺经穴的双向调节效应,观察可视化功能调节的研究,对于针刺双向调节效应机制研究具有特殊意义。研究目的：
在综合回顾并分析文献的基础上,通过观察针刺太溪穴对阿尔茨海默病(Alzheimet's Disease, AD)大鼠模型及轻度认知功能障碍(Mild Cognitive Impairment, MCI)患者病理状态的脑功能代谢的效应,并且经穴与非经穴进行对照,从动物实验到临床患者,从脑功能葡萄糖及血氧代谢正负激活效应角度,观察针刺太溪穴的双向调节中枢效应规律及机制。
研究方法：
以痴呆病作为研究载体,选取肾经原穴太溪作为研究穴位,遵循随机对照的研究原则,动物实验,采用D-半乳糖腹腔注射结合双侧大脑基底核注射鹅膏蕈氨酸(Ibotenic acid, IBO)的复合AD大鼠模型的造模方法,运用小动物PET技术,观察针刺太溪穴对复合AD大鼠模型脑区葡萄糖代谢的正/负激活效应。采用Y迷宫测试大鼠记忆能力,迷宫数据采取重复测量方差分析；临床试验,选取轻度认知障碍患者作为研究对象,采用大脑静息状态fMRI的技术,首先观察其与记忆力正常老年人的比较,病理状态下大脑静息状态fMRI的表现,明确病理状态脑区的血氧代谢水平；并与非经穴进行对照,观察针刺MCI患者太溪穴的脑血氧代谢的正/负激活效应。脑功能成像数据采用基于体素分析法的统计参数图软件SPM2进行分析。
研究结果：
动物实验,AD模型大鼠同时表现出衰老和胆记忆力下降的病理特点。表现了行动迟缓、毛发稀疏等老化征象,并且Y迷宫测试,模型组大鼠较正常组大鼠学习记忆功能下降。脑功能成像方面,模型组大鼠与正常组大鼠经SPM统计比较,既存在右侧顶叶感觉皮质、左侧纹状体及伏核葡萄糖代谢降低的脑区,又存在葡萄糖代谢增高的右侧中脑：被盖、终纹床核、脑桥被盖、中脑上丘、背侧丘脑外侧核群、下丘脑视前区、胼胝体及左侧脑桥被盖、顶叶感觉皮层等脑区。针对AD模型大鼠葡萄糖代谢异常的病理状态,针刺太溪穴对于降低的脑区有使葡萄糖代谢增高的正激活效应,对于增高的脑区有使葡萄糖代谢降低的负激活效应,体现了双向良性调节效应。同时针刺非经非穴也存在一定的靶向双向良性调节,但这种作用,太溪穴较非经穴更明显。
临床研究,MCI患者与正常组健康老人fMRI静息状态比较,血氧代谢降低的脑区集中于：左侧大脑额叶额上回(BA6区)、边缘叶扣带回(BA24区)及颞叶颞上回(BA38区)。未发现MCI患者血氧代谢增高的脑区。针刺MCI患者太溪穴对血氧代谢降低的脑区额叶额上回(BA6区)有正激活效应,同时也较为广泛地激活了学习记忆相关的脑区,如额叶、顶叶、颞叶、岛叶等。针刺非经穴对于左侧顶叶中央后回、顶下小叶(BA40)及左侧颞叶颞上回(BA22)有正激活效应。太溪穴及非经穴均未发现负激活效应。
研究结论：
针刺太溪穴在脑功能代谢调节方面具有双向调节作用,体现在正负激活效应,即对于代谢高的病变脑区有负激活效应,对于代谢低的病变脑区有正激活效应。相较于临床实验,动物实验体现的双向调节作用更明显,体现了双向调节作用与机体病理状态密切相关；与针刺非经非穴比较,针刺经穴的双向良性调节作用具有特异性；同时经穴的双向良性调节具有整体性,即对于代谢异常脑区,针刺经穴的双向调节作用机制是点对面的关系,存在靶向激活与广泛激活的双重效应,靶向效应体现了经穴治疗效应的特异性,广泛效应体现了中医针灸学整体调节的理论特色,一定程度上验证了经穴双向良性调节作用与脑功能相关假说的合理性。
Background
The bidirectional regulation of acupuncture was to adjust the balance of excitatory and inhibitory states. The ultimate aim was to adjust the abnormal pathological state back to or tend to normal physiological state of our body, which is the same as'harmonious state of Yin and Yang'in basic theory of TCM. The bidirectional regulation of acupuncture is one of the important characteristics of the basic theory of Acupuncture. Acupuncture, as a clinical therapy for treatment, has a history of thousands of years, but its therapeutic mechanism is still not clear. The study of bidirectional regulation of acupuncture has always been an important research project.
The effect of bidirectional regulation of acupuncture has a close relationship with acupoint speciality, acupoints compatibility, functional status of body, stimulating method of acupuncture and treatment opportunity. Functional status of body was the basis of bidirectional adjusting function of acupuncture.
Acupuncturing at the special point, as a form of output stimulation, may activate specific part of central nervous system firstly, then controls our nerves, endocrine and fluid network, and influences the target organs finally. A lot of researches have already confirmed that peripheral organs had a close relationship with brain. Pro. LAI Xinsheng put forward:"acupoints-brain relation hypothesis"—Human body as an organism, the reaction and regulating action of acupuncture for target organs should through the adjustment and integration of our central system—brain (transportation and transformation of information), thus realize the treatment effect. On that basis, the bidirectional benign adjustment was an therapeutic effect of acupuncturing at acupoint, which was showed in the central level. That means it has close correlation between bidirectional benign adjustment of acupuncturing and brain.
The21st century is "the century of the brain". Brain Science is the world's scientific frontier. The great progress of brain technology have created favorable conditions for the exploring of the secret effect between acupoints and brain. With the development of functional brain imaging techniques, especially for the technology of positron emission tomography and functional magnetic resonance imaging have become more and more mature, the study of acupuncture on central system entered a new field. Unl i ke the previous technology, cerebral function imaging could be used for the study of acupuncture on brain functional state dynamically, which is in non-invasive state, and in the level of living and holistic and achieve functional visualization. In the brain functional imaging techniques, positive and negative activation of brain could reflect function adjusting state of our brain, from which we can observe the bidirectional benign adjustment of acupuncturing at acupoint. Functional visualization method has special significance in the mechanism study of acupuncture.
Objective
To observe the effect of acupuncture KI6on cerebral function imaging in AD model rats and MCI patients on the basis of systematic review of the literature. Compared acupoint with nonacupoint, from animal experiment to clinical trails, from the perspective of positive and negative activation of brain functional metabolism to observe the central effect rule and mechanism of bidirectional benign adjustment of acupuncturing at KI3.
Methods
Pathological state of the memory decline as a research vehicle. Yuan (source) point in the kidney meridian of Foot Shaoyin-KI3as study points. Randomized controlled rule was followed in this study. In animal experiments, the small animal PET technique and compound AD rat model, which was established by intraperitoneal injection of D-galactose and bilateral nbM injection of Ibotenic acid(IBO), were adopted. In clinical trial, to observe the difference of the brain resting state fMRI between MCI patients and normal people, in order to identify the blood oxygenation level in pathological brain regions. Then to observe the influence of twisting Taixi (KI3) on the brain functional magnetic resonance imaging, and compare with sham point, to deeper elucidate the specificities of acupuncture at acupoints KI3in pathological states. To observe the effect of acupuncture at acupoints KI3and nonacupoint on brain glucose metabolism in AD rat model. Statistical analysis, the Y-maze data was analyzed by the method of repetitive measure anova, and the imaga data was analyzed by SPM2based on voxel-based analysis method.
Results
In animal experiments, the compound AD rats appeared pathological characteristics of aging and meynert nucleus damaged:slow-moving, hypotrichosis and learning and memory decline. On brain activity, compared with normal group, the level of glucose metabolism of model group rats decreased significantly in right parietal Lobe (sensory cortex), left striatum and accumbens nucleus, and increased obviously in right mesencephalon: tegmentum, bed nucleus of stria terminalis, pons:tegmentum, mesencephalon: superior colliculus, dorsal Thalamus:lateral nucleus group, hypothalamus: preoptic region, corpus callosum, left pons:tegmentum and parietal lobe (sensory cortex). Acupuncture at righe KI3of AD mordel rats could activate the low glucose metabolism brain regions, and decrease the high glucose metabolism brain regions. Compared with nonacupoint group, this effect was more obvious.
In clinical trial, on the one hand, in the rest state of fMRI, compared with normal group, the level of the blood oxygenation metabolism In MCI group patients decreased significantly in frontal lobe(BA6), limbic lobe(BA24) and temporal lobe(BA38). No increased metabolism of brain regions were found.at the same time, acupuncture at KI3activated not only the pathological region (BA6), but also other regions, such as frontal lobe, parietal lobe, temporal lobe and insula. Acupuncture at sham point activated some barin regions, such as parietal lobe (BA40) and temporal lobe(BA22). Negative activation of brain regions were not found in KI3and model groups.
Conclusion
Acupuncturing at KI3has bidirectional benign adjustment on brain functional metabolism, which was expressed in positive and negative activation of brain. That means it could reduce the high metabolism of brain regions and activate the low metabolism of brain regions. Compared to the nonacupoint, the bidirectional benign adjustment of KI3was obvious and holistic, which was like the relationship from point to side, and had double effects:targeting activation and wide activation. This targeting effect indicated the specificities of acupoints for treatment effect, and wide effect showed the concept of holism, which was the basic characteristic of acupunture in TCM. These results confirm the validity of "acupoints-brain relation hypothesis" to some degree.
针刺的双向调节作用是通过针刺经穴,使机体或靶器官由异常兴奋状态得到抑制,由异常的抑制状态得到兴奋,或其他层次上的改变,最终目的是使机体由异常的病理状态恢复到或趋向于正常的生理状态或达到一个新的平衡状态,等同于中医基础理论所强调的“阴平阳秘”状态。针刺经穴双向调节作用是针灸作用重要特点之一,但其规律与机理目前还未得到明确的解释,针刺的双向调节作用研究也是近年来针灸作用规律研究的重要方向。
针刺的双向调节效应与腧穴的穴性、腧穴的配伍、机体所处的机能状态、针刺刺激的方式及治疗时机等密切相关。其中,机体的状态是针刺双向调节作用发挥的基础。人体是一个物质、能量、信息的集合体,针刺腧穴对机体的双向调节效应依赖于腧穴自身的物质基础,通过激发调节这些物质,使我们机体对于自身状态产生反馈效应,达到物质、能量与信息的传递交流。
针刺腧穴作为一个外在刺激可能首先激活了相应的中枢神经系统,通过中枢神经系统而调控神经、内分泌、免疫网络,继而影响靶效应器官。现代医学已经积累了大量的外周器官与大脑相互联系的证据。导师赖新生教授提出了“经穴效应与脑相关”的假说。他认为人体作为一个生物体,针刺穴位干预的反应和调节作用必须经过脑作为中枢的调节和整合(即信息的传导和转导),再作用于靶效应器官,从而实现治疗效应。在此基础上,针刺经穴位的双向良性调节作用是经穴治疗效应的体现,在中枢脑层面也应该有所体现,即：经穴双向良性调节作用与脑相关。
21世纪是“脑的世纪”,脑科学是全世界科学的前沿学科。脑科学相关技术的巨大发展为揭示经穴脑效应的奥妙创造了有利的客观条件。随着脑功能成像技术的发展,尤其是功能磁共振成像(functional magnetic resonance imaging, fMRI)和正电子发射层成像(positron emission tomography, PET)等技术日益发展,针刺腧穴对脑中枢效应的研究进入了崭新的领域。与以往生化及物理技术不同的是,脑功能成像技术可以在无创状态下,动态地在活体和从整体水平上来研究针刺经穴对脑功能状态的调节效应,实现功能的可视化。脑功能成像技术中,正激活与负激活的概念反映了机体大脑功能调节状态,从正负激活角度观察针刺经穴的双向调节效应,观察可视化功能调节的研究,对于针刺双向调节效应机制研究具有特殊意义。研究目的：
在综合回顾并分析文献的基础上,通过观察针刺太溪穴对阿尔茨海默病(Alzheimet's Disease, AD)大鼠模型及轻度认知功能障碍(Mild Cognitive Impairment, MCI)患者病理状态的脑功能代谢的效应,并且经穴与非经穴进行对照,从动物实验到临床患者,从脑功能葡萄糖及血氧代谢正负激活效应角度,观察针刺太溪穴的双向调节中枢效应规律及机制。
研究方法：
以痴呆病作为研究载体,选取肾经原穴太溪作为研究穴位,遵循随机对照的研究原则,动物实验,采用D-半乳糖腹腔注射结合双侧大脑基底核注射鹅膏蕈氨酸(Ibotenic acid, IBO)的复合AD大鼠模型的造模方法,运用小动物PET技术,观察针刺太溪穴对复合AD大鼠模型脑区葡萄糖代谢的正/负激活效应。采用Y迷宫测试大鼠记忆能力,迷宫数据采取重复测量方差分析；临床试验,选取轻度认知障碍患者作为研究对象,采用大脑静息状态fMRI的技术,首先观察其与记忆力正常老年人的比较,病理状态下大脑静息状态fMRI的表现,明确病理状态脑区的血氧代谢水平；并与非经穴进行对照,观察针刺MCI患者太溪穴的脑血氧代谢的正/负激活效应。脑功能成像数据采用基于体素分析法的统计参数图软件SPM2进行分析。
研究结果：
动物实验,AD模型大鼠同时表现出衰老和胆记忆力下降的病理特点。表现了行动迟缓、毛发稀疏等老化征象,并且Y迷宫测试,模型组大鼠较正常组大鼠学习记忆功能下降。脑功能成像方面,模型组大鼠与正常组大鼠经SPM统计比较,既存在右侧顶叶感觉皮质、左侧纹状体及伏核葡萄糖代谢降低的脑区,又存在葡萄糖代谢增高的右侧中脑：被盖、终纹床核、脑桥被盖、中脑上丘、背侧丘脑外侧核群、下丘脑视前区、胼胝体及左侧脑桥被盖、顶叶感觉皮层等脑区。针对AD模型大鼠葡萄糖代谢异常的病理状态,针刺太溪穴对于降低的脑区有使葡萄糖代谢增高的正激活效应,对于增高的脑区有使葡萄糖代谢降低的负激活效应,体现了双向良性调节效应。同时针刺非经非穴也存在一定的靶向双向良性调节,但这种作用,太溪穴较非经穴更明显。
临床研究,MCI患者与正常组健康老人fMRI静息状态比较,血氧代谢降低的脑区集中于：左侧大脑额叶额上回(BA6区)、边缘叶扣带回(BA24区)及颞叶颞上回(BA38区)。未发现MCI患者血氧代谢增高的脑区。针刺MCI患者太溪穴对血氧代谢降低的脑区额叶额上回(BA6区)有正激活效应,同时也较为广泛地激活了学习记忆相关的脑区,如额叶、顶叶、颞叶、岛叶等。针刺非经穴对于左侧顶叶中央后回、顶下小叶(BA40)及左侧颞叶颞上回(BA22)有正激活效应。太溪穴及非经穴均未发现负激活效应。
研究结论：
针刺太溪穴在脑功能代谢调节方面具有双向调节作用,体现在正负激活效应,即对于代谢高的病变脑区有负激活效应,对于代谢低的病变脑区有正激活效应。相较于临床实验,动物实验体现的双向调节作用更明显,体现了双向调节作用与机体病理状态密切相关；与针刺非经非穴比较,针刺经穴的双向良性调节作用具有特异性；同时经穴的双向良性调节具有整体性,即对于代谢异常脑区,针刺经穴的双向调节作用机制是点对面的关系,存在靶向激活与广泛激活的双重效应,靶向效应体现了经穴治疗效应的特异性,广泛效应体现了中医针灸学整体调节的理论特色,一定程度上验证了经穴双向良性调节作用与脑功能相关假说的合理性。
Background
The bidirectional regulation of acupuncture was to adjust the balance of excitatory and inhibitory states. The ultimate aim was to adjust the abnormal pathological state back to or tend to normal physiological state of our body, which is the same as'harmonious state of Yin and Yang'in basic theory of TCM. The bidirectional regulation of acupuncture is one of the important characteristics of the basic theory of Acupuncture. Acupuncture, as a clinical therapy for treatment, has a history of thousands of years, but its therapeutic mechanism is still not clear. The study of bidirectional regulation of acupuncture has always been an important research project.
The effect of bidirectional regulation of acupuncture has a close relationship with acupoint speciality, acupoints compatibility, functional status of body, stimulating method of acupuncture and treatment opportunity. Functional status of body was the basis of bidirectional adjusting function of acupuncture.
Acupuncturing at the special point, as a form of output stimulation, may activate specific part of central nervous system firstly, then controls our nerves, endocrine and fluid network, and influences the target organs finally. A lot of researches have already confirmed that peripheral organs had a close relationship with brain. Pro. LAI Xinsheng put forward:"acupoints-brain relation hypothesis"—Human body as an organism, the reaction and regulating action of acupuncture for target organs should through the adjustment and integration of our central system—brain (transportation and transformation of information), thus realize the treatment effect. On that basis, the bidirectional benign adjustment was an therapeutic effect of acupuncturing at acupoint, which was showed in the central level. That means it has close correlation between bidirectional benign adjustment of acupuncturing and brain.
The21st century is "the century of the brain". Brain Science is the world's scientific frontier. The great progress of brain technology have created favorable conditions for the exploring of the secret effect between acupoints and brain. With the development of functional brain imaging techniques, especially for the technology of positron emission tomography and functional magnetic resonance imaging have become more and more mature, the study of acupuncture on central system entered a new field. Unl i ke the previous technology, cerebral function imaging could be used for the study of acupuncture on brain functional state dynamically, which is in non-invasive state, and in the level of living and holistic and achieve functional visualization. In the brain functional imaging techniques, positive and negative activation of brain could reflect function adjusting state of our brain, from which we can observe the bidirectional benign adjustment of acupuncturing at acupoint. Functional visualization method has special significance in the mechanism study of acupuncture.
Objective
To observe the effect of acupuncture KI6on cerebral function imaging in AD model rats and MCI patients on the basis of systematic review of the literature. Compared acupoint with nonacupoint, from animal experiment to clinical trails, from the perspective of positive and negative activation of brain functional metabolism to observe the central effect rule and mechanism of bidirectional benign adjustment of acupuncturing at KI3.
Methods
Pathological state of the memory decline as a research vehicle. Yuan (source) point in the kidney meridian of Foot Shaoyin-KI3as study points. Randomized controlled rule was followed in this study. In animal experiments, the small animal PET technique and compound AD rat model, which was established by intraperitoneal injection of D-galactose and bilateral nbM injection of Ibotenic acid(IBO), were adopted. In clinical trial, to observe the difference of the brain resting state fMRI between MCI patients and normal people, in order to identify the blood oxygenation level in pathological brain regions. Then to observe the influence of twisting Taixi (KI3) on the brain functional magnetic resonance imaging, and compare with sham point, to deeper elucidate the specificities of acupuncture at acupoints KI3in pathological states. To observe the effect of acupuncture at acupoints KI3and nonacupoint on brain glucose metabolism in AD rat model. Statistical analysis, the Y-maze data was analyzed by the method of repetitive measure anova, and the imaga data was analyzed by SPM2based on voxel-based analysis method.
Results
In animal experiments, the compound AD rats appeared pathological characteristics of aging and meynert nucleus damaged:slow-moving, hypotrichosis and learning and memory decline. On brain activity, compared with normal group, the level of glucose metabolism of model group rats decreased significantly in right parietal Lobe (sensory cortex), left striatum and accumbens nucleus, and increased obviously in right mesencephalon: tegmentum, bed nucleus of stria terminalis, pons:tegmentum, mesencephalon: superior colliculus, dorsal Thalamus:lateral nucleus group, hypothalamus: preoptic region, corpus callosum, left pons:tegmentum and parietal lobe (sensory cortex). Acupuncture at righe KI3of AD mordel rats could activate the low glucose metabolism brain regions, and decrease the high glucose metabolism brain regions. Compared with nonacupoint group, this effect was more obvious.
In clinical trial, on the one hand, in the rest state of fMRI, compared with normal group, the level of the blood oxygenation metabolism In MCI group patients decreased significantly in frontal lobe(BA6), limbic lobe(BA24) and temporal lobe(BA38). No increased metabolism of brain regions were found.at the same time, acupuncture at KI3activated not only the pathological region (BA6), but also other regions, such as frontal lobe, parietal lobe, temporal lobe and insula. Acupuncture at sham point activated some barin regions, such as parietal lobe (BA40) and temporal lobe(BA22). Negative activation of brain regions were not found in KI3and model groups.
Conclusion
Acupuncturing at KI3has bidirectional benign adjustment on brain functional metabolism, which was expressed in positive and negative activation of brain. That means it could reduce the high metabolism of brain regions and activate the low metabolism of brain regions. Compared to the nonacupoint, the bidirectional benign adjustment of KI3was obvious and holistic, which was like the relationship from point to side, and had double effects:targeting activation and wide activation. This targeting effect indicated the specificities of acupoints for treatment effect, and wide effect showed the concept of holism, which was the basic characteristic of acupunture in TCM. These results confirm the validity of "acupoints-brain relation hypothesis" to some degree.
引文
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