CAJ | 학술논문

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。目的：研究石榴皮多酚有效部位對小鼠單次給藥毒性，評價其安全性，為新藥研髮和臨床用藥提供理論依據。觀察石榴皮多酚有效部位對無水乙醇緻大鼠胃潰瘍的保護作用。方法選擇健康昆明種小鼠50隻，隨機分為5組，每組10隻，分彆灌胃給予不同劑量的石榴皮多酚有效部位，連續觀察14 d，每日記錄各組小鼠一般情況、毒性反應及死亡情況，採用Bliss 法計算半數緻死量。選擇健康大鼠70隻，隨機分為：正常組、模型組（等體積生理鹽水）、三九胃泰顆粒組（1850 mg·kg－1）、枸櫞痠鉍鉀組（33 mg·kg－1）和石榴皮多酚有效部位低、中、高劑量組（430、852、1704 mg · kg－1），連續灌胃10 d；d 10，除正常組外，其餘各組採用無水乙醇灌胃（每隻1.5 mL）緻大鼠胃潰瘍；計算各組胃潰瘍指數、潰瘍抑製率、觀察胃黏膜組織形態學改變、測定胃黏膜組織中PGE2、NO、SOD、MDA含量。結果石榴皮多酚有效部位的半數緻死量（LD50）為8520.9 mg·kg－1，其95％的可信限範圍為（7291.2～9914.4）mg·kg－1；病理學顯示，給藥劑量為16000 mg·kg－1的小鼠髒器有不同程度的損傷。實驗錶明，與模型組比較，石榴皮多酚有效部位對胃黏膜損傷有明顯脩複作用，且明顯升高胃潰瘍大鼠胃黏膜NO含量、提高胃潰瘍大鼠胃黏膜 SOD 活性及降低 MDA 含量、增加PGE2含量。結論石榴皮多酚有效部位給藥劑量為5063 mg·kg－1未齣現死亡，隨著石榴皮多酚有效部位給藥劑量的增加，給藥劑量為16000 mg·kg－1可造成小鼠的心、肝、肺、腎髒有不同程度的損傷，甚至導緻死亡。石榴皮多酚有效部位的LD50為8520.9 mg·kg－1，其95％的可信限範圍為（7291.2～9914.4）mg·kg－1。石榴皮多酚有效部位對無水乙醇緻大鼠胃潰瘍具有良好的保護作用，這種作用可能與促進胃潰瘍上皮細胞閤成、提高再生黏膜功能、增彊抗氧化能力和誘導、促進NO閤成有關。
목적：연구석류피다분유효부위대소서단차급약독성，평개기안전성，위신약연발화림상용약제공이론의거。관찰석류피다분유효부위대무수을순치대서위궤양적보호작용。방법선택건강곤명충소서50지，수궤분위5조，매조10지，분별관위급여불동제량적석류피다분유효부위，련속관찰14 d，매일기록각조소서일반정황、독성반응급사망정황，채용Bliss 법계산반수치사량。선택건강대서70지，수궤분위：정상조、모형조（등체적생리염수）、삼구위태과립조（1850 mg·kg－1）、구연산필갑조（33 mg·kg－1）화석류피다분유효부위저、중、고제량조（430、852、1704 mg · kg－1），련속관위10 d；d 10，제정상조외，기여각조채용무수을순관위（매지1.5 mL）치대서위궤양；계산각조위궤양지수、궤양억제솔、관찰위점막조직형태학개변、측정위점막조직중PGE2、NO、SOD、MDA함량。결과석류피다분유효부위적반수치사량（LD50）위8520.9 mg·kg－1，기95％적가신한범위위（7291.2～9914.4）mg·kg－1；병이학현시，급약제량위16000 mg·kg－1적소서장기유불동정도적손상。실험표명，여모형조비교，석류피다분유효부위대위점막손상유명현수복작용，차명현승고위궤양대서위점막NO함량、제고위궤양대서위점막 SOD 활성급강저 MDA 함량、증가PGE2함량。결론석류피다분유효부위급약제량위5063 mg·kg－1미출현사망，수착석류피다분유효부위급약제량적증가，급약제량위16000 mg·kg－1가조성소서적심、간、폐、신장유불동정도적손상，심지도치사망。석류피다분유효부위적LD50위8520.9 mg·kg－1，기95％적가신한범위위（7291.2～9914.4）mg·kg－1。석류피다분유효부위대무수을순치대서위궤양구유량호적보호작용，저충작용가능여촉진위궤양상피세포합성、제고재생점막공능、증강항양화능력화유도、촉진NO합성유관。
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.