Lambrecht N, Trautmann M, Korolkiewicz R, Liszkay M, Peskar B M
Department of Experimental Clinical Medicine, Ruhr-University of Bochum, Germany.
Gut. 1993 Mar;34(3):329-37. doi: 10.1136/gut.34.3.329.
The mechanism underlying the mucosal protective effect of antacids is still unclear. This study shows that in rats the aluminum containing antacid, hydrotalcit, induces dose dependent protection against gastric mucosal damage caused by ethanol or indomethacin which is considerably enhanced by acidification. Hydrotalcit did not increase gastric mucosal formation or the intraluminal release of prostaglandins, and did not prevent the increase in mucosal leukotriene C4 formation in response to ethanol. Pretreatment with indomethacin did not attenuate the protective effect of unmodified or acidified hydrotalcit. Furthermore, hydrotalcit significantly reduced the gastric damage caused by indomethacin even when it was administered up to 2 hours after the ulcerogen. In indomethacin treated rats, simultaneous administration of hydrotalcit did not affect the concentrations of indomethacin in serum or inflammatory exudates nor did it attenuate the inhibition of prostaglandin release into the exudates. In hydrotalcit treated rats there was no attenuation of the increase in sulphidopeptide leukotriene release or decrease in leukocyte influx into inflammatory exudates elicited by indomethacin administration. Functional ablation of afferent neurons and inhibition of endogenous nitric oxide partially antagonised the protective effect of unmodified, but not of acidified, hydrotalcit. It is concluded that (i) the protective effect of unmodified and acidified hydrotalcit is independent of the eicosanoid system; (ii) protection against indomethacin induced gastric lesions does not require treatment before dosing of the ulcerogen and does not interfere with absorption and anti-inflammatory actions of indomethacin; (iii) endogenous nitric oxide and afferent neurons contribute partly to the effect of unmodified, but not of acidified, hydrotalcit suggesting that different mechanisms mediate their mucosal protective activity.
抗酸剂黏膜保护作用的潜在机制仍不清楚。本研究表明，在大鼠中，含铝抗酸剂水滑石可诱导剂量依赖性地保护胃黏膜免受乙醇或吲哚美辛所致损伤，酸化可显著增强这种保护作用。水滑石不会增加胃黏膜前列腺素的生成或腔内释放，也不能防止乙醇诱导的黏膜白三烯C4生成增加。用吲哚美辛预处理不会减弱未修饰或酸化水滑石的保护作用。此外，即使在给予致溃疡剂后2小时给药，水滑石仍能显著减轻吲哚美辛所致的胃损伤。在吲哚美辛处理的大鼠中，同时给予水滑石不影响血清或炎性渗出物中吲哚美辛的浓度，也不会减弱对前列腺素释放到渗出物中的抑制作用。在用吲哚美辛诱导炎性渗出物的水滑石处理的大鼠中，硫肽白三烯释放增加或白细胞流入减少没有减弱。传入神经元的功能消除和内源性一氧化氮的抑制部分拮抗了未修饰但非酸化水滑石的保护作用。结论是：（i）未修饰和酸化水滑石的保护作用独立于类花生酸系统；（ii）预防吲哚美辛诱导的胃损伤不需要在给予致溃疡剂之前进行处理，且不干扰吲哚美辛的吸收和抗炎作用；（iii）内源性一氧化氮和传入神经元部分促成了未修饰但非酸化水滑石的作用，这表明不同机制介导了它们的黏膜保护活性。
