ラット実験潰瘍とPAF(platelet-activating factor,血小板活性化因子)

胃内在性PAFの動態とPAF拮抗剤の効果

抄録

Platelet-activating factor (PAF,1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a ether-linked phospholipid that exhibits a wide range of biological activities, that include stimulation of platelet and neutrophile, vasodilation, increase in vascular permeability, bronchoconstriction and pulmonary hypertension. Such actions have implicated PAF as a potent chemical mediator in anaphylactic or inflammatory processes. Furthermore, in recent studies, it has been elucidated that PAF was not only produced in response to pathological stimulation but also generated in normal animal tissues. But, it remains to be unclear what is the biological role of the endogenous PAF in normal tissues.
On the other hand, there have also been many reports on gastric mucosal damage induced by exogenous PAF or protective effect of PAF antagonist in experimental ulcer model. However, these observations suggested that stomach was the target organ for PAF which contributed to pathological state (e. g. inflammation).
This study focussed the relation between endogenou s PAF in stomach and the alteration of gastric microenvironment and suggested the following matters.
1) It was elucidated that the endogenous PAF was indeed present in stomach of normal rat. The significantly high level of PAF was detected in the antrum.
2) The endogenous PAF level dynamically altered in quick resp onse to stimuli which affected the gastric microenvironment (e. g. water-immersion stress).
3) It was suggested that PAF might play some role in the formation or deterioration of gastric mucosal lesion induced by water-immersion stress and ethanol, because the specific PAF antagonists prevented such experimental ulcer.
4) It was also suggested that the endogen ous PAF level in stomach was changed in association with physiological alteration, aging.
Stomach maintains its homeostasis by many kinds of factors. PAF may play some biological role as one of such factors. Hence, the alteration of endogenous PAF level may cause the imbalance of gastric microenvironment which contributed to the etiopathogenesis in gastric mucosal lesion (especially in the early phase of ulceration), or may be expression of senescence.