本文選題：長航疲勞 + 模型�。� 參考：《北京中醫(yī)藥大學》2017年碩士論文

【摘要】：長航疲勞是指海上長期航行過程中由于過度的工作負荷、緊張的心理因素、惡劣的環(huán)境等引起的作業(yè)效率明顯降低的一種生理心理現象。與長期單一工作、海上特殊環(huán)境和生活作息狀態(tài)等因素有關,臨床表現多體現在"身體、神經感覺、精神"三個方面。長航疲勞發(fā)生率有報道高達85.6%,目前已逐漸成為導致長航人員工作能力和健康狀況下降的主要原因,甚至會導致重大事故。目前國內外對長航疲勞主要以臨床研究的形式進行,因此有必要建立長航疲勞動物模型,對其發(fā)生發(fā)展機制進行深入研究。本文就長航疲勞問題,從理論方面對長航疲勞進行綜述,在實驗研究方面建立長航疲勞動物模型,探索其生理機制,為預防和治療長航疲勞提供思路和方法。理論研究:理論一:通過對國內外長航疲勞相關文獻進行歸納整理,總結長航疲勞總體表現為主觀疲勞感、不良情緒和認知功能下降三個方面。導致長航疲勞的因素復雜多樣,歸納起來主要有長航環(huán)境惡劣、飲食作息不規(guī)律以及生理不調和社會心理因素等方面。正是由于長航疲勞的特殊性,目前對長航疲勞的治療主要以療養(yǎng)和補充為主,并無針對長航疲勞的動物模型和有效藥。因此,建立長航疲勞動物模型,開發(fā)有效藥物很有必要。理論二:對疲勞所致負面情緒心理的現代研究進展進行綜述,疲勞所致負面情緒的產生普遍存在,其發(fā)生發(fā)展與多個腦區(qū)相關,主要有海馬、杏仁核、前額葉皮質等。其機理復雜,包括多巴胺獎勵機制、下丘腦-垂體-腎上腺軸(HPA)軸紊亂、5-HT代謝失常、GABA/GLU通路失衡等。并對目前具有治療調節(jié)作用的中西醫(yī)治療方法進行闡述,中醫(yī)藥療效卓著,值得進一步研究推廣。實驗一:長航疲勞大鼠模型裝置——水面晃動站臺儀的創(chuàng)制目的:創(chuàng)制長航疲勞大鼠模型裝置。方法:采用傳統(tǒng)水環(huán)境小平臺配合浮動因素,創(chuàng)制高度模擬長航環(huán)境的大鼠模型裝置。通過大量模擬實驗,尋求滿足實驗要求的模型標準,委托生產商進行加工制作。結果:經過多次摸索改良,由我方提供規(guī)格參數,委托北京科立怡德科技有限公司加工生產,創(chuàng)制了符合要求的長航疲勞大鼠模型裝置——水面晃動站臺儀。實驗二:長航疲勞大鼠造模條件的選擇目的:為建立長航疲勞大鼠模型選擇合適的造浪功率。方法:選12只大鼠進行適應性喂養(yǎng)和適應性站臺后,觀察記錄此組大鼠每只在造浪器以0轉/min,65轉/min,85轉/min和100轉/min造浪時的修飾時間,然后統(tǒng)計分析。結果:與0轉/min時相比,100轉/min時大鼠的修飾時間明顯縮短,差異性非常顯著(P0.01);65轉/min和85轉/min時大鼠站臺的修飾時間略有增加和減少,差異性均不顯著(P0.05)。與65轉/min時相比,85轉/min時修飾時間略有減少,差異不明顯(P0.05),而100轉/min時大鼠的修飾時間明顯縮短,差異性非常顯著(P0.01)。結論:造浪器以85轉/min時大鼠受有影響,但無明顯的情緒改變,是長航疲勞大鼠模型建立的最適宜條件。實驗三:長航疲勞大鼠模型相關證候探索目的:建立長航疲勞大鼠模型,并對其進行探索。方法:基于站立傳統(tǒng)水環(huán)境小平臺復制大鼠疲勞模型的方法,以每日站立傳統(tǒng)水環(huán)境小平臺10h,浮動站臺2h,持續(xù)21天的方法建立長航疲勞大鼠模型,以負重力竭游泳實驗、曠場實驗和大鼠懸尾實驗等行為學實驗,合血乳酸、肌酸激酶、血清D-木糖,血清皮質酮含量等的變化,并與單純站立水環(huán)境小平臺的疲勞模型大鼠對比,綜合評判長航疲勞模型大鼠特征。結果:①體重變化:正常對照組大鼠體重平穩(wěn)增長,傳統(tǒng)平臺組體重早期增長較慢,后與正常對照組持平,而浮臺模型組體重最低。②一次性力竭游泳結果:浮臺模型組力竭時間與正常組相比顯著縮短(P0.05),與傳統(tǒng)平臺組相比差異不顯著(P0.05)。③懸尾實驗結果:傳統(tǒng)平臺組與浮臺模型組懸尾不動時間較正常組均顯著延長(P0.05)。④曠場實驗結果:大鼠修飾時間以浮臺模型組最長,與正常對照組相比差異不顯著(p0.05),而明顯多于傳統(tǒng)平臺組(P0.05)。大鼠在曠場中直立次數以浮臺模型組最少,與正常對照組和傳統(tǒng)平臺組相比均明顯減少,差異顯著(p0.05);傳統(tǒng)平臺組較正常對照組直立次數減少,但差異不顯著(P0.05)。⑤血乳酸、UREA、CK結果:與正常組相比,浮臺模型組血乳酸含量明顯增高,差異顯著(P0.05);傳統(tǒng)平臺組血乳酸含量高于正常組,但差異不顯著(P0.05)。大鼠血清UREA含量,傳統(tǒng)平臺組與正常對照組相比差異顯著(P0.05);浮臺模型組與正常對照組相比差異極其顯著(P0.01),與傳統(tǒng)平臺組相比差異不明顯(P0.05)。血清CK含量,浮臺模型組明顯高于正常對照組,差異顯著(P0.05);傳統(tǒng)平臺組與浮臺模型組和正常對照組相比均無顯著差異(P0.05)。⑥血清CORT、ACTH含量:兩模型組均明顯高于正常對照組(P0.05,P0.05),模型組之間無明顯差異。⑦血清5-HT含量:浮臺模型組明顯高于傳統(tǒng)平臺組和正常對照組(P0.05,P0.01),傳統(tǒng)平臺組與正常對照組之間差異不明顯(P0.05)。⑧血清D-木糖含量:浮臺模型組血清D-木糖明顯低于正常對照組,且差異顯著(P0.05);與傳統(tǒng)平臺組無明顯差異。結論:長航疲勞模型大鼠不僅充分具有疲勞表現,并且腸胃消化吸收能力較弱,情緒反應也一定程度上受到影響,有傾向抑郁的表現。實驗四:體復康加減方對長航疲勞模型大鼠的調節(jié)作用及模型證候驗證目的:觀察"體復康加減方"對長航疲勞模型大鼠的調節(jié)作用。方法:選用"體復康加減方"對長航疲勞模型大鼠進行干預,并以四逆散和西藥輔酶Q10作為對照藥物,研究其對長航疲勞模型大鼠的治療作用并進一步探索模型的特點。結果:"體復康加減方"對長航疲勞模型大鼠負重游泳能力、曠場實驗大鼠興奮性和大鼠懸尾實驗等行為學均有明顯改善,對大鼠血乳酸、UREA、5-HT/血清D-木糖、CORT含量也起到一定調節(jié)作用。結論:"體復康加減方"對長航疲勞模型大鼠療效顯著,也從側面支持了長航疲勞模型大鼠的中醫(yī)證候屬性為肝郁脾虛。實驗五:長航疲勞模型大鼠海馬單胺類神經遞質變化及中藥干預作用目的:體復康加減方對長航疲勞模型大鼠海馬單胺類神經遞質的影響,探討藥物作用機制。方法:取實驗四大鼠海馬組織,采用高效液相電化學檢測法檢測5-HT、DA、NE含量。結果:浮臺模型組大鼠海馬5-HT含量明顯低于空白對照組,差異顯著(P0.05),各用藥組大鼠海馬5-HT含量均較浮臺模型組有所提高;各用藥組之間,用藥組與空白對照組之間無明顯差異(P0.05)。DA和NE含量,浮臺模型組與空白對照組和各用藥組相比均無顯著性差異(P0.05)。結論:長航疲勞模型大鼠存在一定抑郁表現,但并未達到可以診斷為抑郁癥的程度,"體復康加減方"對長航疲勞大鼠模型情緒的調節(jié)可能是通過改善海馬5-HT的含量發(fā)揮療效。小結綜合以上結論可知:一、長航疲勞大鼠模型具有明顯的抑郁的負面情緒。二、體復康加減方對長航疲勞大鼠模型的疲勞表現和負面情緒具有明顯的改善作用。三、長航疲勞模型大鼠存在一定抑郁表現,但并未達到可以診斷為抑郁癥的程度,"體復康加減方"可以通過調整海馬5-HT的含量對長航疲勞模型大鼠抑郁情緒進行調節(jié)從而發(fā)揮治療作用。
[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.
【學位授予單位】：北京中醫(yī)藥大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R259

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