JP2010266238A - Fatigue degree determination method and fatigue degree determination kit - Google Patents
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Abstract
Description
本発明は、ヒトの疲労度の判定方法に関する。より詳しくは、ヒトの血液中のα−メラノサイト刺激ホルモンの濃度を指標としてヒトの疲労度を判定する方法に関する。 The present invention relates to a method for determining the degree of human fatigue. More specifically, the present invention relates to a method for determining human fatigue using the concentration of α-melanocyte stimulating hormone in human blood as an index.
疲労感や倦怠感は、日常的に誰もが経験している感覚であり、『体がだるい』という訴えは、毎年、厚生労働省の「国民生活基礎調査」の有訴者率の上位にランクされている。 Fatigue and fatigue are the feelings that everybody experiences on a daily basis, and the complaint of “both bodily” ranks high in the accused rate in the “National Life Basic Survey” of the Ministry of Health, Labor and Welfare every year. Has been.
１９８５年の健康に関する国民意識調査では、調査時に疲労感を認めた人が６６．４％にのぼる。その７１．７％の人は「１晩の睡眠により疲労感は回復する」と回答しており、疲労・倦怠感は、短期的なものであり、慢性疲労はごくまれなものと思われてきた。しかし、１９９８年に厚生労働省の疲労調査研究班が愛知県豊川保健所管内の１５〜６５歳の男女４０００名に疫学調査を行ったところ、疲労感を自覚している人の割合は約６０％であり、その半数を超える人々（全体の３５．８％）が半年以上続く慢性疲労を認め、５人に１人は作業能力の低下を感じていることも判明した。 In the national attitude survey on health in 1985, 66.4% recognized fatigue at the time of the survey. 71.7% of respondents replied that “an overnight sleep recovers fatigue.” Fatigue / malaise is short-term, and chronic fatigue seems to be rare. It was. However, in 1998, when the Fatigue Research Group of the Ministry of Health, Labor and Welfare conducted an epidemiological survey of 4,000 men and women aged 15 to 65 in the Toyokawa Public Health Center in Aichi Prefecture, the proportion of those who were aware of fatigue was about 60%. Yes, more than half (35.8% of the total) found chronic fatigue lasting more than half a year, and it was also found that one in five felt a decline in work capacity.
“倦怠感”を主訴とする場合、臨床的には（１）器質的疾患（悪性腫瘍、感染症、内分泌・代謝性疾患等）、（２）非器質的疾患（気分障害、身体表現性障害等）、（３）過労（疲れて当然と思われる状況がある）、（４）心配状態（病気を心配しているが、異常のないことを保証すると安心して症状がなくなる）、（５）原因不明の慢性疲労に分けられる。 When “Fatigue” is the main complaint, clinically (1) organic diseases (malignant tumors, infectious diseases, endocrine / metabolic diseases, etc.), (2) non-organic diseases (mood disorders, physical expression disorders) Etc.), (3) Overworked (there is a situation that seems natural due to fatigue), (4) Worried state (I am worried about the illness, but if I guarantee that there is no abnormality, the symptoms disappear without worry), (5) It is divided into chronic fatigue of unknown cause.
ここで、“慢性疲労”とは、半年以上の期間続く自覚的な疲労感すべてを意味し、疲労感の程度や疲労感以外の症状の有無、病気に罹患しているか否かなどは関係しない。したがって、日常生活にはまったく支障をきたさない程度のごく軽い疲労感でも、半年以上の期間続いている場合には慢性疲労と呼ばれる。一方、原因不明の慢性疲労の中には、“慢性疲労症候群（ＣＦＳ）”が含まれる。 Here, “chronic fatigue” means any subjective fatigue that lasts for more than half a year, regardless of the degree of fatigue, the presence or absence of symptoms other than fatigue, and whether or not you are ill. . Therefore, even if the fatigue level is only slight enough not to interfere with daily life, it is called chronic fatigue if it lasts for more than half a year. On the other hand, “chronic fatigue syndrome (CFS)” is included in chronic fatigue of unknown cause.
慢性疲労症候群を客観的に評価することが行われている（例えば、特許文献１参照）。この文献では、被験者の末梢血中のメッセンジャーＲＮＡを用いて、特定のマーカー遺伝子の発現を解析している。しかし、この方法では、慢性疲労全般を評価することができない。 An objective evaluation of chronic fatigue syndrome has been performed (see, for example, Patent Document 1). In this document, the expression of a specific marker gene is analyzed using messenger RNA in the peripheral blood of a subject. However, this method cannot evaluate overall chronic fatigue.
また、「疲労」を簡潔かつ客観的に評価する方法が開発されている（例えば、特許文献２参照）。この文献では、体液中のアシルカルチニンの濃度を測定して、疲労度を評価している。しかし、この文献に記載の方法で評価する疲労度は、急性疲労であることが好ましいとされている。 In addition, a method for simply and objectively evaluating “fatigue” has been developed (see, for example, Patent Document 2). In this document, the degree of fatigue is evaluated by measuring the concentration of acylcarcinin in body fluids. However, the degree of fatigue evaluated by the method described in this document is preferably acute fatigue.
このように、慢性疲労全般を簡潔かつ客観的に評価する方法は、開発されていない。従って、慢性疲労全般を簡潔かつ客観的に評価する方法の開発が望まれる。
本発明は、上記問題に鑑みなされたものであり、その目的は、慢性疲労全般を簡潔かつ客観的に評価する方法を提供することにある。 The present invention has been made in view of the above problems, and an object thereof is to provide a method for simply and objectively evaluating overall chronic fatigue.
本発明者らは、慢性ストレスモデルラットを用い、長期にストレスを与えたラットでは、下垂体中間葉に存在するメラノトロフが活性化し、α−メラノサイト刺激ホルモン（以下、「α−ＭＳＨ」という）の血液濃度が上昇することを見出している。しかし、実験動物にストレスを負荷することと、ヒトが疲労することとは同義ではない。 The present inventors used a chronic stress model rat, and in a rat subjected to stress for a long time, melanotroph present in the pituitary intermediate lobe is activated, and α-melanocyte stimulating hormone (hereinafter referred to as “α-MSH”) is activated. It has been found that blood concentration increases. However, stressing laboratory animals is not synonymous with human fatigue.
また、本発明者らは、自らを被験者として、急性疲労の状態における血液中のα−ＭＳＨの濃度を確認したところ、α−ＭＳＨの上昇は認められなかった。一方、慢性疲労状態にある被験者においては、血液中のα−ＭＳＨの濃度が上昇することを見出し、本発明を完成した。すなわち、本発明は以下のとおりである。 Moreover, when the present inventors confirmed the density | concentration of the alpha-MSH in the blood in the state of acute fatigue by making themselves into a test subject, the raise of alpha-MSH was not recognized. On the other hand, in subjects who are in a chronic fatigue state, the present inventors have found that the concentration of α-MSH in the blood increases and completed the present invention. That is, the present invention is as follows.
本発明の慢性疲労度の判定方法は、被験者の血液中のα−ＭＳＨの濃度を指標として、被験者の慢性疲労度を判定するものである。 The method for determining the degree of chronic fatigue of the present invention is to determine the degree of chronic fatigue of a subject using the concentration of α-MSH in the blood of the subject as an index.
上記判定方法において、α−ＭＳＨの濃度が高いと、慢性疲労度が高いと判定する。 In the above determination method, when the concentration of α-MSH is high, it is determined that the degree of chronic fatigue is high.
上記判定方法において、上記慢性疲労度は、慢性疲労または慢性疲労症候群に基づく過労状態である。 In the determination method, the degree of chronic fatigue is an overworked state based on chronic fatigue or chronic fatigue syndrome.
本発明は、上記の慢性疲労度の判定方法を実施するための慢性疲労度判定キットである。 The present invention is a chronic fatigue level determination kit for carrying out the above-described chronic fatigue level determination method.
本発明の慢性疲労度の判定方法は、被験者の血液中のα−ＭＳＨの濃度を指標として、被験者の慢性疲労度を判定する。被験者の血液中の成分であるため、被験者の負担も少ない。また、血液中のα−ＭＳＨの濃度を測定することで、慢性疲労度を簡便かつ正確に測定することができる。 The method for determining the degree of chronic fatigue according to the present invention determines the degree of chronic fatigue of a subject using the concentration of α-MSH in the blood of the subject as an index. Since it is a component in the blood of the subject, the burden on the subject is small. Further, by measuring the concentration of α-MSH in blood, the degree of chronic fatigue can be measured easily and accurately.
以下に、本発明を詳細に説明する。本発明の慢性疲労度の判定方法は、被験者の血液中のα−ＭＳＨの濃度を指標として、被験者の慢性疲労度を判定するものである。 The present invention is described in detail below. The method for determining the degree of chronic fatigue of the present invention is to determine the degree of chronic fatigue of a subject using the concentration of α-MSH in the blood of the subject as an index.
（慢性疲労度）
本明細書で、「慢性疲労度」とは、上記した“慢性疲労症候群（ＣＦＳ）”を含む原因不明の慢性疲労を意味する。また、本発明の慢性疲労度の判定方法で検出できる慢性疲労度としては、疲労感を自覚して５年以内の疲労度に適用できる。なお、“慢性疲労”とは、上記したように、半年以上の期間続く自覚的な疲労感を意味するが、半年未満であっても半年近傍の期間続く自覚的な疲労感も含めるものとする。
(Chronic fatigue)
In the present specification, the “chronic fatigue level” means chronic fatigue of unknown cause including the above-mentioned “chronic fatigue syndrome (CFS)”. Further, the chronic fatigue level that can be detected by the method for determining the chronic fatigue level of the present invention can be applied to a fatigue level within 5 years of consciousness of fatigue. As described above, “chronic fatigue” means subjective fatigue that lasts for more than half a year, but also includes subjective fatigue that lasts for a period of around half a year even if it is less than half a year. .
（α−メラノサイト刺激ホルモン）
α−メラノサイト刺激ホルモン（α−ＭＳＨ）は、副腎皮質刺激ホルモン（ＡＣＴＨ）のＮ末端部分の１３個のアミノ酸からなるペプチドであり、そのＮ末端がアセチル化され、Ｃ末端がアミド化されている。
(Α-melanocyte stimulating hormone)
α-melanocyte-stimulating hormone (α-MSH) is a peptide consisting of 13 amino acids in the N-terminal part of adrenocorticotropic hormone (ACTH), and its N-terminus is acetylated and its C-terminus is amidated. .
α−ＭＳＨは、例えば動物がストレスを受けた際に、視床下部−脳下垂体−副腎皮質が介在して生産されるホルモンである。ストレスを受けた場合に、最初に視床下部において副腎皮質刺激ホルモン放出因子（ＣＲＦ）が放出される。これが刺激となり、脳下垂体においてプロピオメラノコルチン（ＰＯＭＣ）が生産される。ＰＯＭＣ遺伝子は、主として下垂体前葉のＡＣＴＨ産生細胞で発現している。ＣＲＦによってＰＯＭＣの発現が誘導さ
れると、プロセシングを受けて、α−ＭＳＨが産生される。
α-MSH is a hormone produced through the intervention of the hypothalamus-pituitary-adrenal cortex when an animal is stressed, for example. When stressed, first the corticotropin releasing factor (CRF) is released in the hypothalamus. This stimulates the production of propiomelanocortin (POMC) in the pituitary gland. The POMC gene is mainly expressed in ACTH-producing cells in the anterior pituitary gland. When the expression of POMC is induced by CRF, it is processed and α-MSH is produced.
通常、ストレスを受けた動物の血液中では、α−ＭＳＨの濃度が上昇する。また、急性疲労のヒトの血液中では、α−ＭＳＨの濃度は上昇しない。一方、原因不明の慢性疲労の場合は、α−ＭＳＨの血中濃度が、上昇する。なお、本明細書中で、「いわゆる慢性疲労ではないヒト」とは、半年以上の期間続く自覚的な疲労感を感じていないヒトまたは慢性疲労症候群が発生していない健康なヒトのことをいう。 Usually, the concentration of α-MSH increases in the blood of a stressed animal. In addition, the concentration of α-MSH does not increase in the blood of humans with acute fatigue. On the other hand, in the case of chronic fatigue of unknown cause, the blood concentration of α-MSH increases. In the present specification, the term “human who is not so-called chronic fatigue” refers to a human who does not feel subjective fatigue that lasts for a period of more than half a year or a healthy human who has not developed chronic fatigue syndrome. .
血液中のα−ＭＳＨの測定は、公知の方法で行えばよい。例えば、放射免疫測定（Ｒａｄｉｏｉｍｍｕｎｏａｓｓａｙ：ＲＩＡ）法、エライザ（Ｅｎｚｙｍｅ−Ｌｉｎｋｅｄ ＩｍｍｕｎｏＳｏｒｂｅｎｔ Ａｓｓａｙ：ＥＬＩＳＡ）法などである。 The measurement of α-MSH in blood may be performed by a known method. For example, there are a radioimmunoassay (RIA) method, an enzyme-linked immunosorbent assay (ELISA) method, and the like.
（慢性疲労度判定キット）
本発明の慢性疲労度判定キットは、ヒトにおける疲労度を評価するキットである。すなわち、上記した本発明の疲労度の判定方法を実施するためのキットであればよい。具体的には、被験者の血液を採取するための手段と、採取後の血液中のα−ＭＳＨの濃度を測定する手段を有するキットであればよい。採取後の血液中のα−ＭＳＨの濃度を測定する手段としては、公知の測定方法を実施する手段である。例えば、上記したα−ＭＳＨの濃度の測定方法に用いる、試薬、器具、装置、触媒などをいう。
(Chronic fatigue assessment kit)
The chronic fatigue level determination kit of the present invention is a kit for evaluating fatigue level in humans. That is, the kit may be any kit for carrying out the above-described fatigue level determination method of the present invention. Specifically, it may be a kit having means for collecting blood of a subject and means for measuring the concentration of α-MSH in the blood after collection. The means for measuring the concentration of α-MSH in the blood after collection is a means for carrying out a known measurement method. For example, it refers to a reagent, instrument, device, catalyst, etc. used in the above-described method for measuring the concentration of α-MSH.
（慢性疲労度の判定方法および慢性疲労度判定キットの利用方法）
本発明の慢性疲労度の判定方法および慢性疲労度判定キットの利用方法は、慢性疲労を自覚して、５年以内のヒトに対して有効である。また、血液中のα−ＭＳＨの濃度を測定するだけで、従来存在しなかった慢性疲労症候群を含む慢性疲労を評価することができる。このため、長期間に渡り継続する過労の蓄積を検出するマーカーとして利用できる。
(Method of judging chronic fatigue level and method of using chronic fatigue level judging kit)
The method for determining the degree of chronic fatigue and the method for using the kit for determining the degree of chronic fatigue of the present invention are effective for humans within 5 years who are aware of chronic fatigue. Moreover, it is possible to evaluate chronic fatigue including chronic fatigue syndrome, which has not existed conventionally, only by measuring the concentration of α-MSH in blood. Therefore, it can be used as a marker for detecting accumulation of overwork that continues for a long period of time.
また、本発明の慢性疲労度の判定方法および慢性疲労度判定キットの利用方法を用いると、長期間に渡り継続する過労の蓄積を検出できる。このため、過労による様々な障害や事故を予防することができる。また、血液中のα−ＭＳＨの濃度を測定することにより、被験者が慢性疲労から回復できる物質等をスクリーニングすることができる。 Further, by using the method for determining the degree of chronic fatigue and the method for using the kit for determining the degree of chronic fatigue of the present invention, it is possible to detect the accumulation of overwork that continues for a long period of time. For this reason, various troubles and accidents due to overwork can be prevented. Further, by measuring the concentration of α-MSH in the blood, it is possible to screen for substances that can be recovered from chronic fatigue by the subject.
なお、本発明の慢性疲労度の判定方法および疲労度判定キットは、血液中のα−ＭＳＨの濃度を測定するだけで、被験者が慢性疲労の状態にあるかどうかを判断することができる。また、この血液中のα−ＭＳＨの濃度の測定も簡便に行える。このため、被験者、実施者のいずれにおいても、負担の少ない方法および定キットを提供することができる。 Note that the method for determining the degree of chronic fatigue and the kit for determining the degree of fatigue according to the present invention can determine whether or not a subject is in a state of chronic fatigue by simply measuring the concentration of α-MSH in blood. In addition, the concentration of α-MSH in the blood can be easily measured. For this reason, both a test subject and a practitioner can provide a method and a fixed kit with less burden.
以下、実施例により本発明を説明するが、本発明はかかる実施例に限定されるものではない。 EXAMPLES Hereinafter, although an Example demonstrates this invention, this invention is not limited to this Example.
（被験者）
大阪市立大学疲労クリニカルセンターにて、慢性疲労症候群と診断され、罹患期間１２０ヶ月以内で、本診断法開発のための研究に参加することについて文章により説明し同意を得た者（５７名）とした。対照群には、各患者に対して、性別比、年齢分布を揃えた健常者（３０名）を用いた。本研究は、大阪市立大学医学部付属病院倫理委員会の承認を得ている。
(subject)
(57 people) who were diagnosed with chronic fatigue syndrome at Osaka City University Fatigue Clinical Center, explained in text and agreed to participate in research for developing this diagnostic method within 120 months did. In the control group, healthy individuals (30 persons) with the same sex ratio and age distribution were used for each patient. This study was approved by the Osaka City University School of Medicine Hospital Ethics Committee.
（α−ＭＳＨの測定）
上記慢性疲労症候群の患者および健常者の血漿を用いて、血漿中のα−ＭＳＨの濃度を以下のように測定した。
(Measurement of α-MSH)
Using the plasma of patients with chronic fatigue syndrome and healthy subjects, the concentration of α-MSH in the plasma was measured as follows.
上記慢性疲労症候群の患者および健常者から、ＥＤＴＡ-２ＮＡａ入り採血管により採血を行った。採血は、午前中、朝食抜きで、医師または看護師が安静下に肘静脈より行った。 Blood was collected from patients with chronic fatigue syndrome and healthy volunteers using a blood collection tube containing EDTA-2NAa. Blood was collected from the elbow vein in the morning without breakfast and with a doctor or nurse resting.
上記採取した血液を、３０００ｒｐｍ（１７００×ｇ）、１０分間、４℃で遠心分離し、上清（血漿）を得た。この血漿を分注し、−８０℃にて保存したものをサンプルとした。 The collected blood was centrifuged at 3000 rpm (1700 × g) for 10 minutes at 4 ° C. to obtain a supernatant (plasma). This plasma was dispensed and stored at −80 ° C. as a sample.
α−ＭＳＨの濃度の測定は、ＲＩＡを用いて行った。具体的には、ＥＵＲＩＡ−α−ＭＳＨ（ＥＵＲＯ−ＤＩＡＧＮＯＳＴＩＣＡ製）を用いて、以下のようにしてα−ＭＳＨの濃度を測定した。 The concentration of α-MSH was measured using RIA. Specifically, the concentration of α-MSH was measured as follows using EURIA-α-MSH (manufactured by EURO-DIAGNOSTICA).
まず、下記表１に示すスタンダード、およびサンプル血漿を準備した。
希釈液はｋｉｔに添付のものを使用
希釈液（Ｒｅａｇｅｎｔ Ｄ）；０．０５Ｍ ｐＨ７．４リン酸緩衝液、０．２５％ヒト血清アルブミン、０．２５％エチレンジアミン四酢酸、０．０５％アジ化ナトリウム、５００ ＫＩＵ／ｍＬ Ｔｒａｓｙｌｏｌ混合液。
Ｓｔａｎｄａｒｄは添付の合成ペプチド（ＳＹＳＭＥＨＦＲＷＧＫＰＶ）を使用
First, the standards shown in Table 1 below and sample plasma were prepared.
Diluent used is kit attached to kit Diluent (Reagent D); 0.05M pH 7.4 phosphate buffer, 0.25% human serum albumin, 0.25% ethylenediaminetetraacetic acid, 0.05% azide Sodium, 500 KIU / mL Trasylol mixture.
Standard uses attached synthetic peptide (SYSMEHFRWGKPV)
標準液、およびサンプル血漿、それぞれ１００μＬをＲＩＡチューブに各２本ずつ入れた。ＮＳＢを除く、ＴＢおよび、ｓｔａｎｄａｒｄ、サンプル血漿の各チューブに抗α−ＭＳＨ抗体希釈液を２００μＬずつ加えボルテックスにより混和した。抗α−ＭＳＨ抗体希釈液（Ｒｅａｇｅｎｔ Ａ）として、ウサギ抗α−ＭＳＨ血清（抗体濃度は不明）、０．０５Ｍ ｐＨ７．４ リン酸緩衝液、０．２５％ヒト血清アルブミン、０．２５％エチレンジアミン四酢酸、０．０５％アジ化ナトリウム、５００ ＫＩＵ／ｍＬ Ｔｒａｓｙｌｏｌ混合液を用いた。 Two 100 μL each of the standard solution and the sample plasma were placed in RIA tubes. 200 μL of anti-α-MSH antibody dilution was added to each tube of TB, standard, and sample plasma except NSB, and mixed by vortexing. As anti-α-MSH antibody diluent (Reagent A), rabbit anti-α-MSH serum (antibody concentration is unknown), 0.05 M pH 7.4 phosphate buffer, 0.25% human serum albumin, 0.25% ethylenediamine A mixture of tetraacetic acid, 0.05% sodium azide, 500 KIU / mL Trasylol was used.
上記各チューブに蓋をして、２０〜２４時間、４℃にて静置した。次に、各チューブに、ダブル抗体ＰＥＧ液を５００μＬずつ加え、ボルテックスで混和した。使用したダブル抗体ＰＥＧ液は、ヤギ抗ウサギ血清を含む（濃度不明）、０．０５Ｍ ｐＨ７．４ リン酸緩衝液、０．２５％ヒト血清アルブミン、０．２５％エチレンジアミン四酢酸、０．０５％アジ化ナトリウム、５．０％（ｗ／ｖ）ポリエチレングリコール６０００ 混合液である。 Each tube was covered and allowed to stand at 4 ° C. for 20-24 hours. Next, 500 μL of the double antibody PEG solution was added to each tube and mixed by vortexing. The double antibody PEG solution used contains goat anti-rabbit serum (concentration unknown), 0.05M pH 7.4 phosphate buffer, 0.25% human serum albumin, 0.25% ethylenediaminetetraacetic acid, 0.05% Sodium azide, 5.0% (w / v) polyethylene glycol 6000 mixed solution.
上記チューブを室温にて３０−６０分間静置した。次に、３０００ｒｐｍ（１７００×ｇ）、４℃、１５分間遠心分離を行い、上清を吸引して排除した。 The tube was left at room temperature for 30-60 minutes. Next, centrifugation was performed at 3000 rpm (1700 × g) and 4 ° C. for 15 minutes, and the supernatant was aspirated and removed.
沈殿物をガンマカウンター（アロカ社ＡＵＴＯ ＷＥＬＬ ＧＡＭＭＡ ＳＹＳＴＥＭ）を用いて、放射活性を測定した。ＮＳＢ、ＴＢ、及びｓｔａｎｄａｒｄより検量線を作成し、解析ソフトＡＬＯＫＡ ＲＩＡ ＳＹＳＴＥＭを用いてサンプルの濃度を算出した。結果を以下に示す。 The radioactivity of the precipitate was measured using a gamma counter (ALOKA AUTO WELL GAMMA SYSTEM). A calibration curve was created from NSB, TB, and standard, and the concentration of the sample was calculated using analysis software ALOKA RIA SYSTEM. The results are shown below.
血漿中α−ＭＳＨ濃度の平均値は、ＣＦＳ群では１８．２±７．４ｐｇ／ｍＬ、コントロール群では１４．５±５．７ｐｇ／ｍＬを示し、ＣＦＳ群のほうが高値を示した（ｔ検定：ｐ＝０．０２）。 The mean plasma α-MSH concentration was 18.2 ± 7.4 pg / mL in the CFS group and 14.5 ± 5.7 pg / mL in the control group, and the CFS group showed a higher value (t test). : P = 0.02).
図１は、血漿中α−ＭＳＨ濃度とＣＦＳ罹病期間との相関を表すグラフである。図１において、横軸はＣＦＳ罹病期間（月）を、縦軸は血漿中のα−ＭＳＨ濃度（ｐｇ／ｍｌ）を示す。図１から、血漿中のα−ＭＳＨ濃度は、罹患期間の経過と共に、低下していくが、罹患期間が６０ヶ月（５年）までは、血漿中のα−ＭＳＨ濃度が高いことがわかる。 FIG. 1 is a graph showing the correlation between plasma α-MSH concentration and CFS disease duration. In FIG. 1, the horizontal axis represents the CFS disease duration (months), and the vertical axis represents the plasma α-MSH concentration (pg / ml). FIG. 1 shows that the α-MSH concentration in plasma decreases with the progress of the disease period, but the plasma α-MSH concentration is high until the disease period is 60 months (5 years).
次に、罹患期間を５年以内と５年から１０年未満の２群にわけて検討した。結果を図２に示す。図２は、慢性疲労症候群罹病期間と血漿α−ＭＳＨ濃度の関係を示すグラフである。図２において、横軸はＣＦＳ罹病期間（年）を、縦軸は血漿中のα−ＭＳＨ濃度（ｐｇ／ｍｌ）を示す。図２から、ＣＦＳ罹病期間が５年以内の群（ｎ＝２７）では２０．７±６．９ｐｇ／ｍＬを示し、健常人の値（１４．５±５．７ｐｇ／ｍＬ）よりも有意に高かった（Ｔｕｋｅｙ−Ｋｒａｍｅｒ ｐ≦０．０１，Ａｎｏｖａ Ｐ＝０．００３）。しかし、ＣＦＳ罹病期間が５年以上の群（１４．４±６．１ｐｇ／ｍＬ）と対照群（図中、「ｈｅａｌｔｈ」）との間には統計的な有意差が認められなかった。 Next, the disease duration was examined in two groups of 5 years or less and 5 to less than 10 years. The results are shown in FIG. FIG. 2 is a graph showing the relationship between chronic fatigue syndrome disease duration and plasma α-MSH concentration. In FIG. 2, the horizontal axis represents the CFS disease duration (years), and the vertical axis represents α-MSH concentration (pg / ml) in plasma. FIG. 2 shows that 20.7 ± 6.9 pg / mL in the group with CFS morbidity within 5 years (n = 27), which is significantly higher than the value of healthy individuals (14.5 ± 5.7 pg / mL). High (Tukey-Kramer p ≦ 0.01, Anova P = 0.003). However, there was no statistically significant difference between the group with CFS disease duration of 5 years or more (14.4 ± 6.1 pg / mL) and the control group (“health” in the figure).
（短期疲労における血液中のα−ＭＳＨなどの挙動）
本発明者らは、自らを被験者として、通常の睡眠をとった状態と、２４時間睡眠なしの状態（短期疲労の状態）における、血液中のα−ＭＳＨ、成長ホルモン（Ｇｒｏｗｔｈ Ｈｏｒｍｏｎｅ）、コルチゾール、ＡＣＴＨの濃度を測定した。成長ホルモン、コルチゾール、ＡＣＴＨの濃度の測定は、α−ＭＳＨと同様に、市販の測定キットを用いて行った。結果を図３に示す。図３は、通常の睡眠をとった状態と、短期疲労状態における血液中のα−ＭＳＨ、成長ホルモン（Ｇｒｏｗｔｈ Ｈｏｒｍｏｎｅ）、コルチゾール、ＡＣＴＨの濃度を測定した結果を示すグラフである。図３において、横軸は通常の睡眠をとった状態と、短期疲労状態を、縦軸はα−ＭＳＨ（図３（Ａ）中、「ｐｇ／ｍＬ」）、成長ホルモン（Ｇｒｏｗｔｈ Ｈｏｒｍｏｎｅ）（図３（Ｂ）中、「ｎｇ／ｍＬ」）、コルチゾール（図３（Ｃ）中、「μｇ／ｍＬ」）、ＡＣＴＨ（図３（Ｄ）中、「ｐｇ／ｍＬ」）のそれぞれの濃度を示す。図３から、短期疲労の場合には、α−ＭＳＨの濃度は変化しないことがわかる。一方、成長ホルモン（Ｇｒｏｗｔｈ Ｈｏｒｍｏｎｅ）の濃度は大きく低下している。このことから、短期疲労の場合には、血中のα−ＭＳＨの濃度に影響を与えないことがわかった。
(Behavior of α-MSH in blood during short-term fatigue)
The present inventors, with themselves as subjects, α-MSH in blood, growth hormone (Growth Hormone), cortisol, in a state of taking a normal sleep and in a state of no sleep for 24 hours (a state of short-term fatigue), The concentration of ACTH was measured. The concentrations of growth hormone, cortisol, and ACTH were measured using a commercially available measurement kit in the same manner as α-MSH. The results are shown in FIG. FIG. 3 is a graph showing the results of measuring the concentrations of α-MSH, growth hormone (Growth Hormone), cortisol, and ACTH in the normal sleep state and short-term fatigue state. In FIG. 3, the horizontal axis represents the state of normal sleep and short-term fatigue, and the vertical axis represents α-MSH (“pg / mL” in FIG. 3A), growth hormone (Growth Hormone) (FIG. 3 (B), “ng / mL”), cortisol (“μg / mL” in FIG. 3 (C)), and ACTH (“pg / mL” in FIG. 3 (D)) are shown. . FIG. 3 shows that the concentration of α-MSH does not change in the case of short-term fatigue. On the other hand, the concentration of growth hormone is greatly reduced. From this, it was found that in the case of short-term fatigue, the concentration of α-MSH in the blood is not affected.
以上の結果から、本発明の評価方法は、発症して５年以内の慢性疲労のマーカーとして用いることができることがわかった。
From the above results, it was found that the evaluation method of the present invention can be used as a marker of chronic fatigue within 5 years of onset.
Claims (4)
A chronic fatigue level determination kit for carrying out the chronic fatigue level determination method according to claim 1.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013237666A (en) * | 2012-04-16 | 2013-11-28 | Daiichi Sankyo Healthcare Co Ltd | Therapeutic and/or prophylactic agent for disease associated with overwork or chronic fatigue |
| WO2015030211A1 (en) * | 2013-08-30 | 2015-03-05 | 独立行政法人理化学研究所 | Fatigue biomarker and use thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013237666A (en) * | 2012-04-16 | 2013-11-28 | Daiichi Sankyo Healthcare Co Ltd | Therapeutic and/or prophylactic agent for disease associated with overwork or chronic fatigue |
| WO2015030211A1 (en) * | 2013-08-30 | 2015-03-05 | 独立行政法人理化学研究所 | Fatigue biomarker and use thereof |
| JPWO2015030211A1 (en) * | 2013-08-30 | 2017-03-02 | 国立研究開発法人理化学研究所 | Fatigue biomarkers and their use |
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