Kishimoto S, Kobuke H, Kobayashi H, Kajiyama G, Miyoshi A
Department of Medicine, Hiroshima University School of Medicine, Japan.
Res Commun Chem Pathol Pharmacol. 1991 Mar;71(3):273-92.
The study investigated whether cimetidine could heal chronic erosive gastritis induced experimentally in rats by the administration of taurocholate for 6 months. Taurocholate gastritis is associated with mucosal erosions, the infiltration of inflammatory cells, reduction of the parietal cell mass, reduction of mucosal thickness, and interstitial fibrosis, a histopathological picture similar to that of human erosive gastritis. Microscopic quantitative morphological studies were used to determine the effect of cimetidine administered freely to rats for two weeks in the form of food containing 0.4 or 0.8% of the agent after the withdrawal of taurocholate. Basal acid secretion was analysed in rats with pyloric ligation 12 hours after withdrawal of the cimetidine-containing food. Basal gastrin levels were determined after a 12-hour fast by radioimmunoassay. The total length of the mucosal erosions was significantly decreased in the cimetidine-treated rats of Group A (cimetidine: 400 mg/kg/day: median 294.6 mm) and Group B (800 mg/kg/day; 225.7 mm) when compared to Group C (control gastritis group; 626.4 mm). Both the grade of inflammatory cell infiltration and fibrosis were also significantly reduced in Groups A and B compared with Group C. The number of parietal cells per unit area (A: 101.0, B: 108.8) and the mucosal thickness of the fundic mucosa (A: 0.610, B: 0.710) and of the antral mucosa (A: 0.220, B: 0.240) were greater in Groups A and B than in Group C (85.1 and 0.52 of the fundic mucosa, 0.170 of the antral mucosa, respectively). Basal acid secretion was significantly inhibited in Groups A and B (31.8 and 26.3 mu Eq/hr/100 g body weight, respectively) when compared to Group C (69.6 mu Eq/hr/100 g body weight). Basal serum gastrin levels were significantly higher in Groups A and B (198.1 and 210.5 pg/ml, respectively) than in Group C (98.7 pg/ml). It was concluded from these results that cimetidine had a curative effect on chronic erosive gastritis induced experimentally by taurocholate. The inhibition of acid and gastrin secretion may play an important role in the mechanism of its action.
该研究调查了西咪替丁是否能治愈通过给大鼠喂食牛磺胆酸盐6个月实验诱导的慢性糜烂性胃炎。牛磺胆酸盐性胃炎与黏膜糜烂、炎症细胞浸润、壁细胞数量减少、黏膜厚度降低以及间质纤维化有关,其组织病理学表现与人糜烂性胃炎相似。在停止喂食牛磺胆酸盐后,采用微观定量形态学研究方法来确定以含0.4%或0.8%该药物的食物形式自由给予大鼠两周的西咪替丁的效果。在停止喂食含西咪替丁的食物12小时后,对幽门结扎的大鼠进行基础胃酸分泌分析。通过放射免疫分析法在禁食12小时后测定基础胃泌素水平。与C组(对照性胃炎组;626.4毫米)相比,A组(西咪替丁:400毫克/千克/天;中位数294.6毫米)和B组(800毫克/千克/天;225.7毫米)经西咪替丁治疗的大鼠黏膜糜烂的总长度显著降低。与C组相比,A组和B组的炎症细胞浸润程度和纤维化程度也显著降低。A组(101.0)和B组(108.8)每单位面积的壁细胞数量以及胃底黏膜厚度(A组:0.610,B组:0.710)和胃窦黏膜厚度(A组:0.220,B组:0.240)均高于C组(胃底黏膜分别为85.1和0.52,胃窦黏膜为0.170)。与C组(69.6微当量/小时/100克体重)相比,A组和B组的基础胃酸分泌受到显著抑制(分别为31.8和26.3微当量/小时/100克体重)。A组和B组的基础血清胃泌素水平(分别为198.1和210.5皮克/毫升)显著高于C组(98.7皮克/毫升)。从这些结果得出结论,西咪替丁对牛磺胆酸盐实验诱导的慢性糜烂性胃炎有治疗作用。胃酸和胃泌素分泌的抑制可能在其作用机制中起重要作用。