胃粘膜防御機構におけるプロスタグランディンの役割

Role of Prostaglandin in Mucosal Defensive Mechanism

要旨　Prostaglandin（PG）はヒトのすべての有核細胞のアラキドン酸から主として形成される．われわれはラット胃粘膜に存在するPG量とその遊離を測定する方法を確立した．その結果，ラットおよびヒトの胃壁において大量のPGE₂あるいはPGI₂が存在することが認められた．indomethacinあるいは水浸拘束ストレスを負荷することにより粘膜PGE₂の著明な減少が認められた．一方，0.25NHCIの胃内投与により粘膜PGE₂は2倍に増加し，壊死惹起物質（0.6NHCI）の投与により惹起される潰瘍の発生を抑制した．tetragastrinはまたPGE₂，I₂を増加させ，同様にその潰瘍の発生を防止した．これらの結果は，酸はcytoprotective PGを増加させ，粘膜を保護する．また，内因性PGは酸に対してnegative feed-backを示すことを示唆する．PGE₂によって胃粘膜血流は増加し，PGF_2αにより減少する．また，indomethacinは容量依存的に血流を低下させる．以上の結果から内因性PGは胃粘膜においてlocal regulatory actionを発揮すると考えられる．胃潰瘍症例において，潰瘍より離れた部位のPGE₂量は健常人のそれと差がないが，しかし，易治性潰瘍の辺縁粘膜のそれは難治性のそれに比して高い値を示した．急性潰瘍，例えば，ポリペクトミー（電気焼灼）後の潰瘍は数日後に治癒した．これらの結果は慢性胃潰瘍の治癒の遷延化に粘膜PGの絶対的ならびに相対的不足が密接に関係していることを示している．

　The prostaglandins (PG) are formed mainly from arachidonic acid by all nucleated cell populations in the human body, and protect the gastric mucosa against various ulcerogens (Fig. 1).

　We established a method for determining mucosal PG and their release from rat stomach. Large amounts of PGE₂ or PGI₂ have been found in the stomach wall of rat and humans (Fig. 2, 3).

　The marked reduction of mucosal PGE₂ was observed following the administration of indomethacin or long time exposure to water-immersion stress. On the other hand, intragastric instillation of 0.25 NHCl increased mucosal PGE₂ by about two times, and inhibited ulcer formation induced by subsequent instillation of a necrotizing agent (0.6 NHCl). Tetragastrin also increased mucosal PGE₂ and PGI₂, and inhibited ulcer formation induced by the necrotizing agent. These results suggest that acid induces those cytoprotective PG and enhances mucosal integrity, and also suggest that endogenously synthesized PG exert negative feed-back against gastric acid secretion (Fig. 4).

　Resting gastric mucosal blood flow was increased by PGE₂ and, on the contrary, decreased by PGF_2α, and it was markedly reduced with indomethacin in adose-related manner. It is suggested that endogenous PG exert local regulatory action in gastric mucosa from above mentioned results (Fig. 5, 6).

　The PGE₂ concentrations in the distant mucosa from ulcer portion in gastric ulcer patients were similar to those in normal subjects. However, those levels in the ulcer margin of patients with tractable ulcer were significantly higher than intractable cases. The PG levels increased in acute ulcers induced by mechanical injury such as electric burning polypectomy, and these ulcers healed within several days. These results indicate that an absolute or relative deficiency of mucosal PG is closely related to the ratardation of healing of chronic ulcers (Fig. 7, 8).