ZLR-8对大鼠胃溃疡愈合的影响及体外一氧化氮释放作用  

Effect of ZLR-8 on the Healing of Gastric Ulcer and NO Releasing in vitro

作　　者：冯晓春[1] 季晖[1] 张奕华[2] 殷志勇[1] 

机构地区：[1]中国药科大学药理学教研室,南京210009 [2]中国药科大学新药研究中心,南京210009

出　　处：《中国药科大学学报》2004年第4期357-360,共4页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目 (No .3 0 2 714 91) ;江苏省自然科学基金资助项目 (No .BK2 0 0 2 119)~~

摘　　要：目的 :观察一氧化氮供体型双氯芬酸钠衍生物ZLR 8对大鼠胃溃疡愈合的影响及其NO释放情况。方法 :采用 6 0 %乙酸诱导大鼠胃溃疡后 ,将大鼠随机分为 6组 :ZLR 8高、中、低剂量组 (2 0 ,10 ,5mg/kg)、双氯芬酸钠组 (DC 5mg/kg)、罗非昔布组 (RC 5mg/kg)和CMC Na阴性对照组 ,术后第 3天开始灌胃给药 ,连续 14d。末次给药后 2 4h打开腹腔 ,经十二指肠给药 1次 ,1h后测量胃黏膜血流量 (GMBF)、溃疡面积、血清和胃黏膜组织中NO含量 ,采用Griess法测定ZLR 8体外NO释放量。结果 :ZLR 8组大鼠GMBF明显增加 ,溃疡面积与CMC Na组没有显著性差异 ,明显小于DC和RC组 ,血清和胃黏膜组织中NO含量显著增加。NO体外释放试验结果表明 ,ZLR 8能在短时间内释放出NO ,6h内维持在一定水平 ,释放比较平缓、而且稳定。结论 :ZLR 8不影响胃溃疡的愈合 ,而DC和RC则明显延迟溃疡愈合 ,其机制可能与ZLR 8释放NO后增加GMBF有关。AIM:ZLR-8 is one of the NO-donor DC which has antiinflammatory properties,the purpose of the present study is to determine if ZLR-8 could influence the healing of a preexisting ulcer and the quantity of NO releasing in vitro.METHOD:After induction of gastric ulcer with 60%(v/v) acetic acid,Sprague-Dawly rats were treated with anti-inflammatory doses of ZLR-8 (20,10,5 mg/kg),diclorenac(5 mg/kg),rofecoxib(5 mg/kg) and CMC-Na for 14 days.Then the abdomens of rats were opened 24 h later after the final oral treatment,following duodenum application of the drugs,the GMBF (Gastric Mucosal Blood Flow) and ulcer area were measured after 1 h;NO levels were determined in both the gastric mucosa and serum of rats.The quantity of NO releasing was determined in vitro by Griess method.RESULT:We observed an increase of GMBF of ZLR-8 group but not DC and RC groups;The ulcer area of ZLR-8 group had no significant difference from CMC-Na while less than DC and RC.The quantity of NO in serum and gastric mucosa significantly increased;Results of NO releasing in vitro shows that ZLR-8 could release NO in a short time and maintain in a level during 6 hours. It released NO slowly and smoothly.CONCLUSION:ZLR-8 has no influence on the healing of gastric ulcer while DC and RC delayed the healing,which is probably due to the increase of GMBF after NO releasing of ZLR-8.

关 键 词：一氧化氮 胃溃疡 大鼠 非甾体抗炎药 

分 类 号：R965.1[医药卫生—药理学]