脳腸相関性と自律神経系からみたFDの病態とその治療(シンポジウム:機能性胃腸症(Functional Dyspepsia)の病態を巡る脳腸相関,2008年,第49回日本心身医学会総会(札幌))  [in Japanese] Association of Brain-gut Axis and the Autonomic Nervous System with the Pathogenesis and its Therapy of Functional Dyspepsia(Symposium/Brain-gut Interaction in the Pathophysiology of Functional Dyspepsia)  [in Japanese]

目的:脳腸相関に鑑みたfunctional dyspepsia(FD)の病態生理として,日常ストレスが関与し,その認知は自律神経系や各種メディエーターを介して,運動機能をはじめとする消化管機能に影響を及ぼし,消化器症状を誘発することが推察される.そこで,ストレス負荷が与える消化管運動機能への影響と,自律神経機能の関与,その治療効果について検討した.方法:8週齢Wistar系雄性ラットに5日間の水浸ストレス負荷を与え,体重,相対臓器重量および血中カテコラミンなど,胃排出能を測定した.FD患者にストレス負荷度を問診し,24時間心拍変動解析を行った.高周波成分(HF:0.15〜0.40Hz)は副交感神経機能を,低周波成分(LF:0.04〜0.15Hz)との比LF/HFは交感神経機能の指標とした.(1)24時間全体,(2)覚醒時,睡眠時の比較,(3)食事負荷,(4)自律神経刺激前後での変動および回復度,(5)ディスペプシア症状程度と相関性について検討した.成績:1)ストレス負荷は,体重・相対胸腺重量を有意に低下させたが,副腎重量は有意に増加した.2)血漿ACTH,コルチコステロン,アドレナリン,ノルアドレナリンは増加し,胃排出時間は短期負荷では遅延し,長期負荷では充進した.3)ストレス負荷24時間では,総グレリンおよびデスアシルグレリンの増加を認め,その後の低下と同時期にアシルグレリンの増加を認めた.4)FD群では,24時間平均での副交感神経機能の有意な低下を認め,相対的交感神経系の亢進状態を示した.5)食後30〜60分の副交感神経系ならびに食後90分以降の交感神経系の変動が,FD群では約半数に認められなかった.6)自律神経作動薬での自律神経系アンバランスと消化器症状の改善効果が認められた.結論:FD症例ではストレス負荷による自律神経系の変動と胃機能不全が存在し,外的刺激に対する修正機能の脆弱性が示唆された.自律神経調節薬の有効性が示された.

Aim: As the pathogenesis of functional dyspepsia (FD) considering brain-gut axis, it is thought that daily stressors affect the autonomic nervous system (ANS), gastrointestinal motility, and various chemical mediators thereafter causing abdominal symptoms. We examined the effects of external stresses on gastric emptying in rats and the association of ANS with FD patients. Methods: 1. We examined various parameters: body weight, relative organ weight, catecholamine levels, and gastric emptying in 8-weeks old rats after water immersion stress restraint for 5 days. 2. We analyzed the 24hrs heart rate variability for FD patients after obtaining the questionnaire of daily stressors: component of high frequency (HF: 0.15-0.40Hz) for parasympathetic function and ratio of component of low frequency (LF: 0.04-0.15Hz) to HF component for sympathetic function. We examined 1) 24hrs balance, 2) changes after meal and cold or mental mathematical stressors, 3) effects of tofisopam, a psychovegetative regulator. Results: Stress significantly decreased body weight and relative weight of thymus, and increased relative weight of adrenal glands. Stress increased serum ACTH, corticosterone, adrenalin, and noradrenalin levels. Gastric emptying was decreased in the early phase of the stress restraint and increased in the late phase. Plasma total and inactive ghrelin levels were increased at 24hrs stress restraint and thereafter gradually decreased. Active ghrelin level began to increase at that time. Basal levels of parasympathetic tone were lower and the levels of sympathetic tone were higher in FD patients compared to those of controls. Parasympathetic tone levels of all controls during 30min after meal were higher than their basal condition. But those levels were increased in about half of FD patients. Sympathetic tone levels from 90 to 120 minutes after meal were increased in almost controls but in half of FD patients. Treatment with tofisopam ameliorated the basal imbalance to the normal balanced levels of ANS followed by improving dyspeptic symptoms of FD patients. Conclusions: Fragility of ANS and external stress may be associated with the gastric emptying and abdominal symptoms in FD patients. Treatment with tofisopam, a psychovegetative regulator, may be effective for FD patients.