Etienne A, Thonier F, Hecquet F, Braquet P
Institut Henri Beaufour Research Laboratories, ZA de Courtaboeuf, Les Ulis, France.
Naunyn Schmiedebergs Arch Pharmacol. 1988 Oct;338(4):422-5. doi: 10.1007/BF00172121.
Platelet-activating factor (PAF) has recently been shown to be a potent ulcerogenic agent in the stomach and intestinal mucosa. Its extract mechanism of action is not yet known although histological studies suggest that vasocongestion is an important feature of PAF-induced damage. We have therefore studied the activity of various agents with different modes of action toward PAF-induced gastrointestinal lesions in the rat (PAF 2 micrograms/kg i.v.; macroscopic lesions of tissue scored 20 min later; arbitrary scale from 0 to 4). Drugs were administered either i.m., s.c. (5 min) or orally (30 min) before PAF injection. PAF-induced gastric lesions were strongly inhibited by the natural PAF-antagonist BN 52021 as well as by atropine sulphate and cimetidine which implicates cholinergic stimulation in the ulcerogenic activity of PAF. The somatostatin analog BIM 23014 was also very potent against PAF, perhaps by reducing the parasympathetic stimulation in the gastric wall as described for somatostatin. Allopurinol, which is a free radical scavenger also almost totally inhibited PAF-induced gastric damage, suggesting that neutrophils are involved in the mucosal lesions. The considerable inhibition of the gastric effects of PAF found in neutrophil-depleted animal supports this hypothesis. Theophylline and disodium cromoglycate, mast cell stabilizing drugs which were also active in our model, could act by protecting mast cell degranulation induced by free radicals released from activated neutrophils. A multifunctional process seems to determine the mucosal gastric damage induced by PAF, but parasympathetic stimulation and neutrophil activation play a major role in this pathology.
血小板活化因子（PAF）最近已被证明是胃和肠黏膜中一种强效的致溃疡因子。尽管组织学研究表明血管充血是PAF诱导损伤的一个重要特征，但其确切的作用机制尚不清楚。因此，我们研究了各种作用方式不同的药物对大鼠PAF诱导的胃肠道损伤的活性（PAF 2微克/千克静脉注射；20分钟后对组织的宏观损伤进行评分；从0到4的任意评分标准）。在注射PAF前，药物通过肌肉注射、皮下注射（5分钟）或口服（30分钟）给药。天然的PAF拮抗剂BN 52021以及硫酸阿托品和西咪替丁能强烈抑制PAF诱导的胃损伤，这表明胆碱能刺激参与了PAF的致溃疡活性。生长抑素类似物BIM 23014对PAF也非常有效，可能是通过减少胃壁中的副交感神经刺激，就像生长抑素所描述的那样。别嘌醇作为一种自由基清除剂，也几乎完全抑制了PAF诱导的胃损伤，这表明中性粒细胞参与了黏膜损伤。在中性粒细胞减少的动物中发现对PAF胃效应的显著抑制支持了这一假设。茶碱和色甘酸钠，这两种在我们的模型中也有活性的肥大细胞稳定剂，可能通过保护由活化的中性粒细胞释放的自由基诱导的肥大细胞脱颗粒而起作用。一个多功能过程似乎决定了PAF诱导的胃黏膜损伤，但副交感神经刺激和中性粒细胞活化在这种病理过程中起主要作用。
