抄録
【目的】六君子湯(TJ-43)は胃排泄能促進,胃粘膜保護作用を有することから,慢性胃腸機能障害に用いられている.近年,小児領域でも胃食道逆流症に対して有用性が認められている.その薬理効果はNOを介した胃平滑筋適応性弛緩反射改善作用により発現するが,小腸運動機能に対する効果は明らかにされていない.そこで筆者らは,TJ-43の小腸運動機能に対する作用を検討した.【対象と方法】体重220〜260gのWistar系雄性ラットを用い,8時間の絶飲食後に以下の実験を行った.実験1):ピオクタニン^[○!R]0.7ml投与群とTJ-43 0,79/kgBW+ピオクタニン^[○!R](総量0.7ml)投与群における投与15,30,45分後の色素小腸移送距離測定.実験2):胃,十二指腸,空腸にストレインゲージフォーストランスデューサー^[○!R]を縫着し,TJ-43(0.3,0.5,0.7g/kgBW)投与後の収縮運動を測定.実験3):TJ-43 0.7g/kgBW投与後の門脈血中ガストリン濃度,NO_2/NO_3濃度測定.【結果】1)TJ-43投与群の色素小腸移送距離は有意に短かった.2)TJ-43投与により,十二指腸,空腸の収縮運動は用量依存性に抑制された.3)TJ-43投与後30分の血清ガストリン,NO_2/NO_3濃度はコントロール群に比して有意な上昇を認めた.NO_2/NO_3濃度の上昇は持続性に認められたが,ガストリン濃度は投与後1時間でコントロール値まで低下していた.【結論】TJ-43は空腹時の小腸運動を抑制し,その機序にはNOを介した平滑筋弛緩作用が関与していることが示唆された.
Purpose: Rikkunshi-to has been widely prescribed for patients with functional dyspepsia. However, its pharmacological actions on intestinal motility are still unknown. This study was conducted to evaluate the effects of Rikkunshi-to on small intestinal motility. Methods: Male Wistar rats weighing 220-260 grams were used. All experiments were performed after 8 hours of fasting. 1) The small intestinal transit rate was measured after the administration of Rikkunshi-to. 2) Male Wistar rats were equipped with force transducers on the stomach, duodenum, and proximal jejunum. Contractile motor activity of the bowel in the interdigestive state was measured following the administration of Rikkunshi-to. 3) The serum gastrin levels and nitrite and nitrate (NOx) levels at the portal vein were also determined. Results: 1) The small intestinal transit rate was significantly inhibited after administration of Rikkunshi-to. 2) Rikkunshi-to (0.3-0.7g/kgBW) obviously reduced the motility index in the duodenum and jejunum in a dose-dependent manner. 3) Both the serum gastrin and NOx levels were significantly increased 30min after the administration of Rikkunshi-to. While the increase of NOx levels was maintained, the gastrin levels returned to the control level after 60min. Conclusion: These results indicate that Rikkunshi-to inhibits small intestinal movement. The mechanism of its inhibition seems to be related to the relaxation of intestinal smooth muscle by nitric oxide. Oral administration of Rikkunshi-to prior to feeding is likely to be useful for extending the retention time of food in the small intestine.
