基于动物实验的长航疲劳中医证候研究及相关负面情绪探讨

发布时间：2018-05-27 14:20

本文选题：长航疲劳 + 模型　；参考：《北京中医药大学》2017年硕士论文

【摘要】：长航疲劳是指海上长期航行过程中由于过度的工作负荷、紧张的心理因素、恶劣的环境等引起的作业效率明显降低的一种生理心理现象。与长期单一工作、海上特殊环境和生活作息状态等因素有关,临床表现多体现在"身体、神经感觉、精神"三个方面。长航疲劳发生率有报道高达85.6%,目前已逐渐成为导致长航人员工作能力和健康状况下降的主要原因,甚至会导致重大事故。目前国内外对长航疲劳主要以临床研究的形式进行,因此有必要建立长航疲劳动物模型,对其发生发展机制进行深入研究。本文就长航疲劳问题,从理论方面对长航疲劳进行综述,在实验研究方面建立长航疲劳动物模型,探索其生理机制,为预防和治疗长航疲劳提供思路和方法。理论研究:理论一:通过对国内外长航疲劳相关文献进行归纳整理,总结长航疲劳总体表现为主观疲劳感、不良情绪和认知功能下降三个方面。导致长航疲劳的因素复杂多样,归纳起来主要有长航环境恶劣、饮食作息不规律以及生理不调和社会心理因素等方面。正是由于长航疲劳的特殊性,目前对长航疲劳的治疗主要以疗养和补充为主,并无针对长航疲劳的动物模型和有效药。因此,建立长航疲劳动物模型,开发有效药物很有必要。理论二:对疲劳所致负面情绪心理的现代研究进展进行综述,疲劳所致负面情绪的产生普遍存在,其发生发展与多个脑区相关,主要有海马、杏仁核、前额叶皮质等。其机理复杂,包括多巴胺奖励机制、下丘脑-垂体-肾上腺轴(HPA)轴紊乱、5-HT代谢失常、GABA/GLU通路失衡等。并对目前具有治疗调节作用的中西医治疗方法进行阐述,中医药疗效卓著,值得进一步研究推广。实验一:长航疲劳大鼠模型装置——水面晃动站台仪的创制目的:创制长航疲劳大鼠模型装置。方法:采用传统水环境小平台配合浮动因素,创制高度模拟长航环境的大鼠模型装置。通过大量模拟实验,寻求满足实验要求的模型标准,委托生产商进行加工制作。结果:经过多次摸索改良,由我方提供规格参数,委托北京科立怡德科技有限公司加工生产,创制了符合要求的长航疲劳大鼠模型装置——水面晃动站台仪。实验二:长航疲劳大鼠造模条件的选择目的:为建立长航疲劳大鼠模型选择合适的造浪功率。方法:选12只大鼠进行适应性喂养和适应性站台后,观察记录此组大鼠每只在造浪器以0转/min,65转/min,85转/min和100转/min造浪时的修饰时间,然后统计分析。结果:与0转/min时相比,100转/min时大鼠的修饰时间明显缩短,差异性非常显著(P0.01);65转/min和85转/min时大鼠站台的修饰时间略有增加和减少,差异性均不显著(P0.05)。与65转/min时相比,85转/min时修饰时间略有减少,差异不明显(P0.05),而100转/min时大鼠的修饰时间明显缩短,差异性非常显著(P0.01)。结论:造浪器以85转/min时大鼠受有影响,但无明显的情绪改变,是长航疲劳大鼠模型建立的最适宜条件。实验三:长航疲劳大鼠模型相关证候探索目的:建立长航疲劳大鼠模型,并对其进行探索。方法:基于站立传统水环境小平台复制大鼠疲劳模型的方法,以每日站立传统水环境小平台10h,浮动站台2h,持续21天的方法建立长航疲劳大鼠模型,以负重力竭游泳实验、旷场实验和大鼠悬尾实验等行为学实验,合血乳酸、肌酸激酶、血清D-木糖,血清皮质酮含量等的变化,并与单纯站立水环境小平台的疲劳模型大鼠对比,综合评判长航疲劳模型大鼠特征。结果:①体重变化:正常对照组大鼠体重平稳增长,传统平台组体重早期增长较慢,后与正常对照组持平,而浮台模型组体重最低。②一次性力竭游泳结果:浮台模型组力竭时间与正常组相比显著缩短(P0.05),与传统平台组相比差异不显著(P0.05)。③悬尾实验结果:传统平台组与浮台模型组悬尾不动时间较正常组均显著延长(P0.05)。④旷场实验结果:大鼠修饰时间以浮台模型组最长,与正常对照组相比差异不显著(p0.05),而明显多于传统平台组(P0.05)。大鼠在旷场中直立次数以浮台模型组最少,与正常对照组和传统平台组相比均明显减少,差异显著(p0.05);传统平台组较正常对照组直立次数减少,但差异不显著(P0.05)。⑤血乳酸、UREA、CK结果:与正常组相比,浮台模型组血乳酸含量明显增高,差异显著(P0.05);传统平台组血乳酸含量高于正常组,但差异不显著(P0.05)。大鼠血清UREA含量,传统平台组与正常对照组相比差异显著(P0.05);浮台模型组与正常对照组相比差异极其显著(P0.01),与传统平台组相比差异不明显(P0.05)。血清CK含量,浮台模型组明显高于正常对照组,差异显著(P0.05);传统平台组与浮台模型组和正常对照组相比均无显著差异(P0.05)。⑥血清CORT、ACTH含量:两模型组均明显高于正常对照组(P0.05,P0.05),模型组之间无明显差异。⑦血清5-HT含量:浮台模型组明显高于传统平台组和正常对照组(P0.05,P0.01),传统平台组与正常对照组之间差异不明显(P0.05)。⑧血清D-木糖含量:浮台模型组血清D-木糖明显低于正常对照组,且差异显著(P0.05);与传统平台组无明显差异。结论:长航疲劳模型大鼠不仅充分具有疲劳表现,并且肠胃消化吸收能力较弱,情绪反应也一定程度上受到影响,有倾向抑郁的表现。实验四:体复康加减方对长航疲劳模型大鼠的调节作用及模型证候验证目的:观察"体复康加减方"对长航疲劳模型大鼠的调节作用。方法:选用"体复康加减方"对长航疲劳模型大鼠进行干预,并以四逆散和西药辅酶Q10作为对照药物,研究其对长航疲劳模型大鼠的治疗作用并进一步探索模型的特点。结果:"体复康加减方"对长航疲劳模型大鼠负重游泳能力、旷场实验大鼠兴奋性和大鼠悬尾实验等行为学均有明显改善,对大鼠血乳酸、UREA、5-HT/血清D-木糖、CORT含量也起到一定调节作用。结论:"体复康加减方"对长航疲劳模型大鼠疗效显著,也从侧面支持了长航疲劳模型大鼠的中医证候属性为肝郁脾虚。实验五:长航疲劳模型大鼠海马单胺类神经递质变化及中药干预作用目的:体复康加减方对长航疲劳模型大鼠海马单胺类神经递质的影响,探讨药物作用机制。方法:取实验四大鼠海马组织,采用高效液相电化学检测法检测5-HT、DA、NE含量。结果:浮台模型组大鼠海马5-HT含量明显低于空白对照组,差异显著(P0.05),各用药组大鼠海马5-HT含量均较浮台模型组有所提高;各用药组之间,用药组与空白对照组之间无明显差异(P0.05)。DA和NE含量,浮台模型组与空白对照组和各用药组相比均无显著性差异(P0.05)。结论:长航疲劳模型大鼠存在一定抑郁表现,但并未达到可以诊断为抑郁症的程度,"体复康加减方"对长航疲劳大鼠模型情绪的调节可能是通过改善海马5-HT的含量发挥疗效。小结综合以上结论可知:一、长航疲劳大鼠模型具有明显的抑郁的负面情绪。二、体复康加减方对长航疲劳大鼠模型的疲劳表现和负面情绪具有明显的改善作用。三、长航疲劳模型大鼠存在一定抑郁表现,但并未达到可以诊断为抑郁症的程度,"体复康加减方"可以通过调整海马5-HT的含量对长航疲劳模型大鼠抑郁情绪进行调节从而发挥治疗作用。
[Abstract]:Long voyage fatigue refers to a physiological and psychological phenomenon, due to excessive working load, stressful psychological factors, and bad environment and so on. It is closely related to long-term single work, marine special environment and life and rest state, and the clinical manifestations are mostly embodied in "body, nerve sensation, essence." There are three aspects of "God". The incidence of long voyage fatigue has been reported to be up to 85.6%, which has gradually become the main cause of the decline in the working ability and health of the long voyage, even leading to major accidents. At present, the fatigue of long voyage is mainly in the form of clinical research. This paper makes a thorough study of the mechanism of life development. In this paper, the fatigue of long voyage is reviewed, and the long endurance fatigue animal model is established in the field of experimental research, and its physiological mechanism is explored to provide ideas and methods for the prevention and treatment of long endurance fatigue. Theory 1: through the literature on the fatigue of long voyage at home and abroad The overall performance of long voyage fatigue is subjective fatigue, bad mood and cognitive decline in three aspects. The factors that lead to long endurance fatigue are complex and diverse, which are mainly due to the bad environment of long voyage, irregular diet, and physiological disharmony of social psychological factors. It is due to the particularity of long endurance fatigue, At present, the treatment of long endurance fatigue mainly consists of recuperation and supplement, and there is no animal model and effective medicine for long endurance fatigue. Therefore, it is necessary to establish long endurance animal model and develop effective drugs. Theory two: a review of the modern research progress on negative emotional psychology caused by fatigue is summarized, and the negative emotion caused by fatigue is common. Existence, its occurrence and development related to a number of brain regions, mainly hippocampus, amygdala, prefrontal cortex, etc. its mechanism is complex, including the dopamine reward mechanism, the hypothalamus pituitary adrenal axis (HPA) axis disorder, the 5-HT metabolism disorder, the imbalance of the GABA/GLU pathway and so on. The efficacy of the drug therapy is worth further research and promotion. Experiment 1: the model device of the long endurance rat model - the creation purpose of the water sloshing platform instrument: to create the long endurance rat model device. Method: using the traditional water environment small platform with the floating factors to create a rat model device with high simulation environment. In search of the model standard to meet the requirements of the experiment, the manufacturer is entrusted with the processing and making. Results: after many groping improvements, we have provided the specification parameters by us, and commissioned the processing and production of Beijing corinyde science and Technology Co., Ltd., created the model device of the long endurance fatigue rat model of the long flight - the water surface sloshing platform instrument. Experiment two: long endurance fatigue rat Selection of model conditions: to select the appropriate wave power for establishing a long endurance rat model. Method: after selecting 12 rats for adaptive feeding and adaptive platform, the modification time of each rat in the wave maker was recorded at 0 /min, 65 /min, 85 /min and 100 /min, and then the results were analyzed with 0 /m. At the time of in, the modification time of the rats was obviously shortened and the difference was very significant (P0.01). The modification time of the rat platform was slightly increased and decreased when 65 /min and 85 /min, and the difference was not significant (P0.05). The modification time of the 85 turn /min was slightly reduced, and the difference was not obvious (P0.05), while the rats were 100 /min at the 85 turn of the /min. The modification time was obviously shortened and the difference was very significant (P0.01). Conclusion: the rats were affected by the wave maker at 85 /min, but there was no obvious emotional change. It was the most suitable condition for the establishment of long endurance fatigue rat model. Experiment three: the research item of the model of long endurance fatigue rat model: establish the long endurance rat model and explore it. Method: Based on the method of standing traditional water environment small platform replicating rat fatigue model, the model of long endurance fatigue rat was established by means of standing traditional water environment small platform 10h and floating platform 2H for 21 days. The behavior experiments of exhausted swimming test, open field experiment and rat suspension test were used, blood lactic acid, creatine kinase, serum D- The changes in the content of xylose and serum corticosterone were compared with the fatigue model rats with simple standing water environment. The results were as follows: (1) the body weight of the normal control group increased steadily, the body weight of the traditional platform group increased slowly in the early stage, and then was equal to the normal control group, and the floating platform model group was the same as the normal control group. The result of exhaustion swimming: the time of exhaustion swimming in the floating platform group was significantly shorter than that of the normal group (P0.05), and there was no significant difference compared with the traditional platform group (P0.05). (3) the suspension tail experiment results of the traditional platform group and the floating platform group were significantly longer than those of the normal group (P0.05). (4) the result of the open field experiment: the rat modification The time was the longest in the floating model group, and there was no significant difference compared with the normal control group (P0.05), but more than the traditional platform group (P0.05). The erect frequency of the rats in the open field was the least in the floating platform group, which was significantly reduced compared with the normal control group and the traditional platform group, and the difference was significant (P0.05); the orthostatic times of the traditional platform group were less than the normal control group. Few, but the difference was not significant (P0.05). Blood lactic acid, UREA, CK results: compared with the normal group, the blood lactic acid content in the floating platform group was significantly higher, the difference was significant (P0.05); the blood lactic acid content in the traditional platform group was higher than that of the normal group, but the difference was not significant (P0.05). The serum UREA content in the rat serum, the traditional platform group was significantly different from the normal control group (P0.05); floating platform was significantly different (P0.05). The difference between the model group and the normal control group was very significant (P0.01), and the difference was not obvious compared with the traditional platform group (P0.05). The serum CK content was significantly higher than that of the normal control group (P0.05). There was no significant difference between the traditional platform group and the floating platform group and the normal control group (P0.05). (6) the serum CORT, ACTH content: two model. The type group was significantly higher than the normal control group (P0.05, P0.05), and there was no significant difference between the model groups. The serum 5-HT content: the floating platform group was significantly higher than the traditional platform group and the normal control group (P0.05, P0.01), the difference between the traditional platform group and the normal control group was not obvious (P0.05). The serum D- xylose content: the serum D- xylose was significantly lower in the floating model group. In the normal control group, the difference was significant (P0.05), and there was no obvious difference from the traditional platform group. Conclusion: the long endurance fatigue model rats not only have full fatigue performance, but also have weak gut digestion and absorption capacity, the emotional response is also affected to some extent, and there is a tendency to depress depression. Experiment four: body Fukang addition and subtraction on long endurance fatigue model rats Objective: To observe the regulating effect of "somatic Fukang plus subtraction" on long endurance fatigue model rats. Methods: the effect of "body Fukang addition and subtraction" on long endurance fatigue model rats was used, and the therapeutic effect of four inverse scatter and Western medicine coenzyme Q10 as the control drug on the long endurance fatigue model rats was studied. The characteristics of the model were explored. Results: "body Fukang plus and subtraction" had a significant improvement on the swimming ability of the long endurance model rats, the excitability of rats in the open field experiment and the tail suspension experiment of rats, and the blood lactic acid, UREA, 5-HT/ serum D- xylose and CORT content in rats. The effect of the model rats was significant, and the TCM syndrome attributes of the long endurance model rats were also supported on the side of the liver depression and spleen deficiency. Experiment five: the change of monoamine neurotransmitters in the hippocampus of the long endurance model rats and the effect of traditional Chinese medicine on the effect of the traditional Chinese medicine on the monoamine neurotransmitters in the hippocampus of the long endurance fatigue model rats. Methods: the hippocampal tissue of four rats was taken and the content of 5-HT, DA and NE was detected by high performance liquid phase electrochemical detection. Results: the content of 5-HT in hippocampus of the rats in the floating model group was significantly lower than that in the blank control group (P0.05). The content of 5-HT in hippocampus of each drug group was higher than that of the floating model group. There was no significant difference (P0.05).DA and NE content between the control group and the blank control group. There was no significant difference between the floating model group and the blank control group and the medication group (P0.05). Conclusion: the long endurance fatigue model rats had certain depression performance, but did not reach the degree of depression. The adjustment of the thread may be by improving the content of the 5-HT in the hippocampus. The conclusion of the summary above is that: first, the long endurance fatigue rat model has obvious depression negative emotions. Two, the body Fukang addition and subtraction side has a significant improvement on the fatigue and negative emotion of the long endurance fatigue rat model. Three, long endurance model rats survive. In a certain degree of depression, but did not reach the degree that can be diagnosed as depression, "body compound and subtraction" can adjust the depression of the long endurance model rats by adjusting the content of 5-HT in the hippocampus to play a therapeutic role.
【学位授予单位】：北京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R259

【参考文献】