Aims To study single dose toxicity of poly-phenols effective parts from Punica granatum,to eval-uate their safety,and thus to provide a theoretical basis for drug development and clinical use.To observe their protective effect on ethanol-induced gastric ulcer in rats.Methods 50 healthy Kunming mice were ran-domly divided into five groups and given different doses of polyphenols’effective parts from Punica granatum via intragastric administration.Toxicity and death in each group of mice were observed and recorded after administration for 14 d.The median lethal dose was calculated by Bliss method.70 rats were randomly di-vided into normal group,model group(constant volume of normal saline),sanjiuweitai particles(1 850 mg· kg-1 )group,colloidal bismuth subcitrate (33 mg · kg-1 )group and polyphenols effective parts from Puni-ca granatum low-dose,medium-dose,high-dose(430, 852,1 704 mg·kg-1 )groups.On the 9th day of 10 days’gavage,all except the normal group were fed ethanol (1.5 mL/only)to induce gastric mucosal inju-ry in rats with acute gastric ulcer.Gastric ulcer index, the rate of ulcer inhibition were calculated for each group.The morphological changes of gastric mucosa were observed.The gastric mucosa levels of PGE2 , NO,SOD and MDA were determined.Results The LD50 and 95%confidence limit of the polyphenols’ef-fective parts from Punica granatum were 8 520.9 mg· kg-1 and 7 291.2 ~9 914.4 mg·kg-1,respectively. Pathology showed that the organs receiving dose of 16 000 mg · kg-1 had different degrees of damage . Compared with the model group,the extract from Puni-ca granatum significantly repaired the gastric mucosa, and significantly increased the gastric mucosa levels of NO and reduced MDA content,and improved SOD content and the levels of PGE2 .Conclousion The dose of 5 063 mg · kg-1 of polyphenols effective part from Punica granatum showed no death.The dose of 16 000 mg · kg-1 of polyphenols effective parts from Punica granatum could cause varying degrees of dam-age in heart,liver,lung,kidney or the death of mice. The LD50 and 95% confidence limit of the polyphenols effective parts from Punica granatum were 8 520.9 mg ·kg-1 and 7 291.2 ~9 914.4 mg·kg-1,respective-ly.The extract from Punica granatum plays a protective role against gastric mucosa damage induced by absolute ethanol,and the mechanism may be related to promo-ting ulcer epithelial cells synthesis,enhancing mucosal regeneration function,regulating NO content and en-hancing antioxidant capacity.%目的：研究石榴皮多酚有效部位对小鼠单次给药毒性，评价其安全性，为新药研发和临床用药提供理论依据。观察石榴皮多酚有效部位对无水乙醇致大鼠胃溃疡的保护作用。方法选择健康昆明种小鼠50只，随机分为5组，每组10只，分别灌胃给予不同剂量的石榴皮多酚有效部位，连续观察14 d，每日记录各组小鼠一般情况、毒性反应及死亡情况，采用Bliss 法计算半数致死量。选择健康大鼠70只，随机分为：正常组、模型组（等体积生理盐水）、三九胃泰颗粒组（1850 mg·kg－1）、枸橼酸铋钾组（33 mg·kg－1）和石榴皮多酚有效部位低、中、高剂量组（430、852、1704 mg · kg－1），连续灌胃10 d；d 10，除正常组外，其余各组采用无水乙醇灌胃（每只1.5 mL）致大鼠胃溃疡；计算各组胃溃疡指数、溃疡抑制率、观察胃黏膜组织形态学改变、测定胃黏膜组织中PGE2、NO、SOD、MDA含量。结果石榴皮多酚有效部位的半数致死量（LD50）为8520.9 mg·kg－1，其95％的可信限范围为（7291.2～9914.4）mg·kg－1；病理学显示，给药剂量为16000 mg·kg－1的小鼠脏器有不同程度的损伤。实验表明，与模型组比较，石榴皮多酚有效部位对胃黏膜损伤有明显修复作用，且明显升高胃溃疡大鼠胃黏膜NO含量、提高胃溃疡大鼠胃黏膜 SOD 活性及降低 MDA 含量、增加PGE2含量。结论石榴皮多酚有效部位给药剂量为5063 mg·kg－1未出现死亡，随着石榴皮多酚有效部位给药剂量的增加，给药剂量为16000 mg·kg－1可造成小鼠的心、肝、肺、肾脏有不同程度的损伤，甚至导致死亡。石榴皮多酚有效部位的LD50为8520.9 mg·kg－1，其95％的可信限范围为（7291.2～9914.4）mg·kg－1。石榴皮多酚有效部位对无水乙醇致大鼠胃溃疡具有良好的保护作用，这种作用可能与促进胃溃疡上皮细胞合成、提高再生黏膜功能、增强抗氧化能力和诱导、促进NO合成有关。
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