Ostrowski J, Pesta J, Linnik D, Butruk E
Department of Gastroenterology, Medical Center of Postgraduate Education, Warszawa, Poland.
J Physiol Pharmacol. 1993 Sep;44(3):273-81.
Mucosal gastric injury was induced in vivo by oral administration of 75% ethanol to rats that were intraperitoneally pretreated with saline (controls), 4 mg/kg of verapamil, 0.4 mg/kg of nifedipine or 160 mg/kg of MgCl2. The glandular stomachs were used for macroscopic and histologic evaluation of mucosal lesions. The gastroprotective effects of substances tested against ethanol-induced mucosal damage in vitro were examined: 1). in rats intraperitoneally pretreated with calcium antagonists and 2). after adding of 10(-4) M verapamil, 10(-6) M nifedipine or 10(-2) M MgCl2 directly to minced gastric mucosa of untreated rats. This effect was measured by DNA synthesis. Gross and histologic evaluation showed that rats pretreated with nifedipine or MgCl2 had significantly decreased ethanol-induced gastric injury compared to controls, whereas those pretreated with verapamil had significantly increased injury. On the contrary, all verapamil, nifedipine and MgCl2 treatments, administrated intraperitoneally or by exposure to an incubation mixture were equally effective in reducing gastric mucosal damage following to ethanol treatment in vitro. We conclude that the differential effects of verapamil and nifedipine on ethanol-damaged gastric mucosa in vivo, but not in vitro, suggests the existence of different actions of these calcium antagonists more on systemic rather than local protective mechanisms, such as gastric mucosal blood flow, mucosal barrier, or cell renewal.
通过给腹腔注射生理盐水（对照组）、4mg/kg维拉帕米、0.4mg/kg硝苯地平或160mg/kg氯化镁预处理的大鼠口服75%乙醇，在体内诱导胃黏膜损伤。取腺胃用于对黏膜损伤进行大体和组织学评估。检测了受试物质对乙醇诱导的体外胃黏膜损伤的胃保护作用：1）. 对腹腔注射钙拮抗剂预处理的大鼠；2）. 将10(-4)M维拉帕米、10(-6)M硝苯地平或10(-2)M氯化镁直接添加到未处理大鼠的切碎胃黏膜后。通过DNA合成来测定这种作用。大体和组织学评估显示，与对照组相比，用硝苯地平或氯化镁预处理的大鼠乙醇诱导的胃损伤显著减轻，而用维拉帕米预处理的大鼠损伤显著增加。相反，腹腔注射或暴露于孵育混合物中的所有维拉帕米、硝苯地平和氯化镁处理在体外乙醇处理后减轻胃黏膜损伤方面同样有效。我们得出结论，维拉帕米和硝苯地平在体内而非体外对乙醇损伤的胃黏膜的不同作用表明，这些钙拮抗剂更多地在全身而非局部保护机制（如胃黏膜血流、黏膜屏障或细胞更新）上存在不同作用。
