| 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 method of whole adjustment, treatment based on syndrome differentiation 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 behavior, peripheral and central mechanisms 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 StudyInstinctive desire is the core of function of liver governs smoothing qi flow (LGSQF). Motivation is the explicit performance of instinctive desire; emotion is the internal driving product of instinctive desire; cognition is the evaluation of instinctive desire; reward is the satisfied feel when unmet demand has been satisfied. Chronic immobilization stress simulates the pathological process of the liver failing to maintain the normal flow of QI and the treatment of Xiaoyao Powder promotes the functional recovery of liver governs smoothing qi flow(LGSQF). The subject begins from the behavior to study the chronic immobilization stress in rats and the instinctive desire motivated acts (feeding, drinking behavior), emotional behaviors (open field experiments and EPM), cognitive behavior (Y-maze) and the reward-related behavior (sucrose intake experiment), thereby better clarifies of the behavior changes caused by chronic immobilization stress and the regulatory role of Xiaoyao Powder, and has further demonstrated the essence meaning of the function of the liver.Stress response is to avoid the dangerous, and stress resilience mechanism is the steady recovery by changing reached steady state. Chronic immobilization stress is the change in neurobiology to avoid dangerous and detrimental to the environment; stress injury is the manifestation of the liver failing to maintain the normal flow of QI or over to abreact the QI, while the Xiaoyao Powder's regulatory role would contribute to the resilience mechanism of stress, and also is the manifestation of function of liver governs smoothing qi flow (LGSQF). Stress injury and stress resilience system is interconnected, and the factors adjusting the stress injury and resilience and the related brain regions and neural circuit are interconnected. So raised the hypothesis that the factors adjusting the stress injury and resilience and the related brain regions and neural circuit were whether the biological basis of the function of liver governs smoothing qi flow (LGSQF).CCK and NPY are concerned with the ingestion abnormal, anxiety-like behavior, depression-related behavior and learning and memory in cognitive behavior caused by stress. These behavioral changes are closely linked with central reward system (anhedonia). Instinct demand is the core of the generated function of liver governs smoothing qi flow (LGSQF); the reward is the embodiment of essence of liver governs smoothing qi flow (LGSQF); therefore, the central neural circuit of reward system may be one of the neural pathways of liver governs smoothing qi flow (LGSQF). The effects of NPY in response to stress include: anti-anxiety, confrontation the CRH effect and the locus coeruleus - norepinephrine system caused by stress and injurying fear memory. And the effects of CRH are in terms of activating fear conduct, strengthening arousal, enhancing autonomic activities, restraining the autonomic nervous system function and lowering reward expectations. The effects Locus coeruleus - norepinephrine system are: alarm functions that are activated by the internal and external threats, increaseing arousal, increasing attention, fear memory formation, and promoting autonomic actions. The brain areas that NPY involves in stress are the amygdala, hippocampus, hypothalamus, saeptum, periaqueductal gray and locus caeruleus. The major mutual features of NPY in response to stress include: reducing the CRH- related effects in amygdala, reducing the distribution rate of locus coeruleus. NPY and recovery mechanisms: Amygdala NPY appropriate increase related with the reduction of the anxiety and depression caused by stress. NPY and the psychopathology mechanisms caused by stress: In the course of stress, low levels of NPY in response to depression and the increase of the vulnerability of PTSD. CCK is closely linked with the reward system modulated by dopamine; acetylcholine, opioid-like substances and CCK modulate the release of dopamine and glutamate; CCK has a depressive effect on reward. Therefore NPY and CCK were associated with the reward system.NPY and CCK are versatility neuropeptides, analyzed by a lot of literature, NPY is a promoting appetite agent, CCK reduces appetite, NPY is related to stress resilience, is a stress protection factor, CCK is a stress injury factor. NPY and CCK whether embody the whole Chinese Yin-yang balance. NPY-CCK balance modulation, the function of liver governs smoothing qi flow (LGSQF) is normal, and NPY and CCK modulation imbalance embodies or the liver failing to maintain the normal flow of QI or over to abreact the QI.Hypothetical imbalance modulation of NPY and CCK system in the central system of reward (stress injury and stress resilience confrontation) may be one of the mechanisms of rats behavioral changes cause by chronic immobilization stress, also demonstrates one of the bases of pathophysiology of the function of liver governs smoothing qi flow (LGSQF) that the brain-gut axis NPY-CCK system. NPY and CCK system in the brain reward system is how to adjust the function of the Liver function? When NPY-CCK reward system in the central modulation imbalances, such as causing the reward systems excessive activated leading to the Liver over to abreact the QI; inhibiting of the reward system causes the liver failing to maintain the normal flow of QI, when balance the function of liver governs smoothing qi flow (LGSQF) is normal.2 Experimental StudiesExperimental study included the effect of Xiaoyao Power on Behavioral in rats with chronic immobilization stress, the ELISA analysis of plasma NPY and CCK concentrations in rat with chronic immobilization stress the adjusting effects of Xiaoyao Power, and using immunohistochemical method, making the six closely linked sites in limbic system and central nervous rewards circuit, in terms of amygdala, hippocampus, frontal cortex, hypothalamus, nucleus accumbens and caudate - putamen as the targets for observation, Xiaoyao Power as the intervention, from the protein level, semi-quantitative and localization detected the changes of NPY and CCK in rat with chronic immobilization stress and the regulatory role of Xiaoyao Power. Discussion on the central mechanisms of stress response, stress damage and stress resilience and the relationship with the function of liver governs smoothing qi flow (LGSQF). The main results are as follows:Behavioral results suggest: Chronic immobilization stress on body weight, food intake and drinking water all were damaged to a certain extent, Xiaoyao Powder has a protective effect. Model group had highest sucrose intake, followed by treatment group, at least is the normal group. But observed from the plotting trends, after the 21st day, the sucrose intake in normal group rose, model group declined, it explained that after the three weeks of chronic immobilization stress, the animals were turned to depression from excited and anxiety. Open field tests observed the changes of spontaneous activity and exploratory behavior of rats in the new environment. Model animals had declined; Xiaoyao Power had eased the physical and mental exhaustion of rats with chronic immobilization stress. EPM reflects anxiety states of the animal models, and Xiaoyao Powder has certain anti-anxiety effect. Y-maze reflects the animal's escape conditioned reflex reaction and learning and memory capability of spatial resolution. In the Y-maze experiment, the correct rate of entering safe arm differenced between the three groups, but without statistical significance. In which model group and the normal group were significant difference, P = 0.026. The correct rate of entering safe arm of Y-maze in model group was highest, the treatment group secondly, the normal group minimum. Suggest further studies to extend the model of time. Immunohistochemical staining results suggest: 21 days of immobilization stress made NPY and CCK expression in the hippocampus and the ARC decline, and increase the expression of them in the treatment group; it suggests that Xiaoyao Powder has a facilitating role in stress resilience. NPY expression in the BLA, PEV, nucleus accumbens and the FCx of model group downregulated while CCK upregulated. It suggested NPY and CCK have different role in the regulation of stress. NPY can promote stress resilience while CCK effects of a stress injury.Plasma ELISA analysis showed that: Compared with the normal group, the plasma concentrations of NPY and CCK in model group were significantly reduced, while compared with the model group, the concentration of them in the treatment group has increased, it notes that Xiaoyao Powder has a promoting role in stress resilience. |
PDF Full Text Request