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|Title:||麥門冬湯對睡眠及褪黑素的影響 = The effect of mai men dong decoction on sleep and melatonin||Authors:||Wong, Hon Fat (黃漢發)||Keywords:||Hong Kong Polytechnic University -- Dissertations
Insomnia -- Treatment
Herbs -- Therapeutic use
|Issue Date:||2012||Publisher:||The Hong Kong Polytechnic University||Abstract:||背景: 傳統中醫學說認為，失眠是由於衛氣不能從陽入陰所引致的。根據這學說，中醫家在這千年以來，發明了不少的失眠經典名方。這些失眠復方的組成，可視為對應相關的五行失調而設的： 如天王補心丹對應心(火)的失調、半夏瀉心湯對應脾胃(土)的失調、六味地黃丸對應腎(水)的失調、酸棗仁湯對應肝(木)的失調。但至今仍沒有失眠復方，是針對肺(金)的失調而設，教學及臨床亦沒有強調肺(金)對睡眠 (寐)的影響。 彭子益於《圓運動的古中醫學》一書中，認為大自然太陽熱力的降沉，是由於「秋氣」收斂降沉之力去達成的。人對應之，則人體熱力的下降，是由「肺」的功能去達成的。據彭子益的認識，麥門冬湯就具有促進「肺」收斂及降沉的功用，他說：「此治肺經金氣不降之法也。」若麥門冬湯可促成「肺」的收斂及降沉；而根據本論文的文獻研究分析，《黃帝內經》所描述的「衛氣」又可由「肺」推動，則麥門冬湯應具有催眠的作用。 近代有關失眠的研究雖然不少，但並無以「肺」或麥門冬湯作為研究失眠的重點。2007年黃曉輝等提出了失眠從「肺」論治的論點。他們主要根據中醫學裡「肺」的功能、生理、病理與肝脾心腎的關係，去闡述從「肺」論治失眠的論點；但並沒有如本文般論述「肺」怎樣參與「衛氣從陽入陰」的過程，或作實驗證實其論點，亦無為「衛氣」的物質性作出假設。 另外經文獻比較後，發現「衛氣」與褪黑素(Melatonin) 有著很多共通之處。因此本人作出了如下假設：《黃帝內經》中描述的「衛氣」概念，有可能相等於現代醫學所發現的內分泌物：褪黑素。 目標: 這實驗研究有關麥門冬湯對戊巴比妥誘發的大鼠睡眠及其對褪黑素的影響。研究麥門冬湯是否可縮短大鼠入睡時間，以及麥門冬湯是否可增加大鼠血中的褪黑素含量。
方法: 實驗一) 30隻體重200±10克的大鼠，隨機地依體重，平均分為三組：空白對照組，單劑量組及雙劑量組。放置在嚴控實驗環境下(氣溫20±2度攝氏，穩定相對濕度約60%，12小時晝夜節律)，兩周後於ZT16:00時 (Zeitgeber Time，授時因子時間)，依不同所屬組別，分別灌胃相當於零量 (空白對照組)、一日人量 (單劑量組)、兩日人量 (雙劑量組) 的麥門冬湯顆粒溶液，連續喂飼6天。在第6天喂飼後的ZT17:00時，在紅光環境下 (<50lux)，於大鼠腹腔注射戊巴比妥 (Pentobarbital Sodium)，以翻正反射 (Righting reflex) 消失作為大鼠入眠指標，記錄大鼠的入眠潛伏期及睡眠時間。 實驗二) 上述30隻大鼠經過「實驗一」後不殺，在嚴控實驗環境下(氣溫20±2度攝氏，穩定相對濕度約60%，12小時晝夜節律)，放置自由飲食一周。隨機地依體重平均分為三組：空白對照組，單劑量組及Sodium Carboxymethyl Cellulose (SCC) 組，再放置一周後 (共兩周洗脫期)，於ZT13:00時，依不同所屬組別，分別灌胃相當於零量 (空白對照組)、相當於一日人量的麥門冬湯顆粒溶液 (單劑量組)、1% 的SCC溶液(SCC 組)，連續灌胃7天。在第6天灌胃後，於ZT14:00時，在紅光環境下 (<50lux)，用乙醚麻醉大鼠，於眼眶後靜脈叢取血液樣本，以Rat Melatonin ELISA kit作血清Melatonin的含量分析。在第7天喂飼後，於ZT14:00時，於大鼠腹腔注射戊巴比妥 (Pentobarbital Sodium)，以翻正反射消失作為大鼠入眠指標，記錄大鼠的入眠潛伏期及睡眠時間。 數據統計分析: 數據以平均值±標準偏差 (mean±SD) 表達。統計軟件SPSS v.13。以獨立樣本單因數變異數分析 (One-way ANOVA) 計算實驗一及二各組結果的差異性，以P值<0.05，95%的信賴區間(Confidence Interval) 決定統計顯著性差異。 結果 實驗一) 與空白對照組比較平均入眠潛伏期，單劑量組 (P<0.001)、雙劑量組 (P<0.05) 有統計學差異。 與空白對照組比較平均睡眠時間，單劑量組及雙劑量組(P>0.05) 無統計學差異。 實驗二) 與空白對照組比較平均入眠潛伏期，單劑量組 (P>0.05)無統計學差異；但SCC組(p<0.05)有統計學差異。 與空白對照組比較平均睡眠時間，單劑量組 (P>0.05)、SCC組(P>0.05) 均無統計學差異。 與空白對照組比較平均褪黑素含量，單劑量組 (P>0.05)無統計學差異；但SCC組(P<0.05)有統計學差異。 總結: 動物實驗一證明，關燈後四小時(ZT16:00時)給予大鼠麥門冬湯顆粒溶液，於關燈後第五小時(ZT17:00時)，可明顯縮短由戊巴比妥誘發的大鼠入眠潛伏期。根據中醫學說，睡眠是衛氣從陽入陰所達成的；而「肺」肅降的功能，具有推動衛氣從陽入陰的能力。此研究結果，為麥門冬湯可作為臨床失眠復方的選擇之一，提供了動物實驗依據。除此以外，這研究亦間接證明瞭麥門冬湯的作用點 "肺" 與睡眠有相關性，彌補了中醫學說二千年以來，有關「肺」、睡眠與相關中藥復方的空白。
Background : According to Traditional Chinese Medicine (TCM), insomnia is due to the failure of Defensive Qi moving from Yang into Yin. Based on this TCM hypothesis, there were several famous insomniac herbal decoctions being invented. These herbal decoctions were formulated according to their corresponding Five-Phases disharmony, for example, Tian Wang Bu Xin Dan corresponding to HEART (Fire) disharmony, Ban Xia Xie Xin Tang corresponding to SPLEEN/STOMACH (Earth), Liu Wei Di Huang Wan corresponding to KIDNEY (Water), Suan Zao Ren Tang corresponding to LIVER (Wood). However, insomniac Chinese herbal decoction, which is related to LUNG (Metal), has never been addressed or emphasized. Literature Review : Peng Zhi Yi, a contemporary TCM Practitioner, in 1950s’ he stated in his book, Circular Motion of Traditional Chinese Medicine (圓運動的古中醫學), the heat of the Sun was lowering by the natural force of autumn season with descending nature. In human, the lowering of heat is achieved by the descending function of LUNG. According to Peng, Mai Men Dong decoction (MMDD) is able to descend LUNG Qi. He stated “this is to treat the qi of LUNG meridian/Metal which fails to descend”. In addition, The Yellow Emperor's Classic of Internal Medicine suggested that LUNG could promote the movement of Defensive Qi, therefore, I speculate that the MMDD could have soporific effect, which shortening the sleep latency. Although, there were many contemporary TCM investigations regarding the insomnia, however, none of them were based on LUNG perspective. In 2007, Wang et. al. stated their opinion that “treating insomnia in regards to Lung”. However, it was solely based on the TCM perspective of LUNG functions, its physiology and pathology and its relationship with LIVER, SPLEEN, HEART and KIDNEY. How LUNG participates in the sleep mechanism (Defensive Qi moving from Yang into Yin), or what was the material base of Defensive Qi has never been discussed. Furthermore, based on the literature review, I found that there are many similarities between Defensive Qi and Melatonin. Therefore, an assumption was made that “The Defensive Qi, a TCM concept, might be equivalent to Melatonin, an endocrine substance just had been discovered 50 years ago. Objective : This study is to investigate the effects of MMDD on pentobarbital-induced sleep in SD-rats, whether, MMDD is able to shorten the sleep onset and increase the blood content of melatonin of the SD-Rats. Methods : Experiment 1) 30 SD-Rats weighted 200±10g were randomly divided into 3 groups according to their body weight–Blank Control, Single-dose and Double-dose groups. Under controlled laboratory environment (Temperature 20±2°C, relative humidity around 60%, 12：12hr dark/light cycle), the rats were orally fed with zero (Blank Control group), one (Single-dose group) or two (Double-dose group) equivalent human daily dosage of MMDD at ZT16:00 (Zeitgeber Time) for 6 days respectively. On the 6th day of the intervention, under the red LED light condition (<50 lux), pentobarbital (50mg/kg) was injected in the rat's peritoneum at ZT17:00. Loss of the righting reflex was used to determine the sleep onset. The sleep latency and total sleep time were recorded. Experiment 2) 30 SD-Rats in Experiment 1 were not scarified. Under controlled laboratory environment (Temperature 20±2°C, relative humidity around 60%, 12：12hr dark/light cycle), they were fed with food and tap water ad libitum for a week. Then they were randomly divided into 3 groups according to their body weight–Blank Control, Single-dose and Sodium Carboxymethyl Cellulose (SCC) groups. Rats were set for an adaptation period for another week (total two weeks). Then they were fed with zero (Blank Control group), one equivalent human daily dosage of MMDD (Single-dose group) or 1% SCC (SCC group) at ZT13:00 for 7 days respectively. On the 6th day, at ZT14:00 under red LED light condition (<50 lux), blood sample were withdrawn for serum melatonin content analysis. On the 7th day, pentobarbital (50mg/kg) was injected in the rat's peritoneum at ZT14:00. Loss of the righting reflex was used to determine the sleep onset. The sleep latency and sleep time were recorded.
Statistical Data Analysis : The presented data are expressed as means ± standard deviation (SD). SPSS v13 was used. One-Way ANOVA was used to compare the mean differences of the above experiments with P<0.05 and 95% confidence interval to determine the statistical significance differences. Results : Experiment 1) The mean sleep latency of the Single-dose group (P < 0.001) was significantly shorter than that of the Blank Control group. There was no significance different in the mean sleep time among three experimental groups. Experiment 2) Only the mean sleep latency of the SCC group (P < 0.05) was significantly longer than that of the Blank Control group. There was no significance different in the mean sleep time among three experimental groups. Only the mean serum melatonin content of the SCC group (P < 0.05) was significantly higher than that of the Blank Control group. Conclusion : The preliminary findings of this animal study successfully demonstrated that administration of a single-dose of MMDD four hours after the light off is able to reduce the pentobarbital-induced sleep latency in SD-rats at the fifth hour after light off. According to the TCM theories, sleep is the result of the Defensive Qi moving from Yang into Yin. The condition of LUNG will affect the moving of the Defensive Qi also. This study has provided an animal evidence for the use of MMDD (TCM dry cough medication) as a choice of hypnotics in future. This study has also completed the missing link (Metal element) of the Five-phases in relation with sleep, which has never been addressed or emphasized over the past two thousand years.
|Description:||xviii, 249 leaves : ill. ; 30 cm.
PolyU Library Call No.: [THS] LG51 .H577M SN 2012 Wong
|URI:||http://hdl.handle.net/10397/5560||Rights:||All rights reserved.|
|Appears in Collections:||Thesis|
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