PAF受体拮抗剂对内毒素血症幼年大鼠胃黏膜NO含量及iNOS表达的影响  

Effect of PAF antagonist on NO content and expression of iNOS in gastric mucosal during endotoxemia in young rats

作　　者：刘春英[1] 李薇[1] 唐英[1] 王丽杰[2] 孙梅[2] 

机构地区：[1]中国人民解放军第二零二医院儿科,辽宁省沈阳市110003 [2]中国医科大学第二临床学院儿科,辽宁省沈阳市110004

出　　处：《世界华人消化杂志》2009年第6期544-548,共5页World Chinese Journal of Digestology

摘　　要：目的:探讨一氧化氮(NO)、诱导型一氧化氮合酶(iNOS)及PAF受体拮抗剂在内毒素(LPS)腹腔注射诱导的幼年大鼠急性胃黏膜损伤中的作用.方法:Wistar大鼠,随机分为对照组、LPS组、PAF受体拮抗剂预防组和治疗组.用内毒素(O55:B5脂多糖)5mg/kgip制备幼年大鼠内毒素血症模型.预防组和治疗组分别于内毒素ip前及ip后0.5h,应用血小板活化因子(PAF)受体拮抗剂BN52021(GinkgolideB)5mg/kgip,同等量生理盐水ip为对照组.于LPS注射后1.5,3,6,24,48,72h处死动物,大体及光学显微镜下观察胃黏膜损伤情况,采用硝酸还原酶的化学比色法测定胃黏膜NO含量;免疫组织化学S-P方法测定胃黏膜iNOS蛋白的表达,半定量RT-PCR法测定胃黏膜iNOSmRNA的表达.结果:LPS组6h胃黏膜损伤最重,黏膜内有出血,核碎裂、固缩,凋亡小体出现;预防组和治疗组改变轻微.LPS组腹腔注射内毒素后6h胃黏膜NO含量最高,此时LPS组较对照组NO含量明显增高(84.37±5.44vs37.37±1.90,P<0.01),预防组和治疗组(40.07±3.42,48.63±3.24)较LPS组明显降低(P<0.01);预防组与治疗组较对照组明显增高(P<0.05).对照组胃黏膜组织未见iNOS蛋白及mRNA的表达;LPS组腹腔注射内毒素后1.5h胃黏膜组织胞质iNOS蛋白表达,6h明显增高,24h最高,48h下降,72h仍未恢复正常;预防组和治疗组3hiNOS蛋白表达,6h明显增高,48h下降,72h同对照组.iNOSmRNA水平的表达变化与iNOS蛋白表达变化趋势相同.结论:PAF受体拮抗剂可下调iNOSmRNA表达水平,减少iNOS蛋白表达,使NO含量下降.从而使NO和iNOS对胃黏膜发挥保护作用.AIM： To investigate the protective effect of NO, iNOS and PAF antagonist in endotoxin-induced acute gastric mucosal injury in young rats.METHODS： Eighteen-day old Wistar rats were randomly divided into normal control, model group, platelet activating factor （PAF） antago- nist prevention group and treatment group. The model of endotoxemia of young rats was established by intraperitoneal injection of endotoxin （5 mg/kg of Oss：B5 lipopolysaccharide, LPS ）. The rats in PAF prevention and treatment groups were administered with PAF antagonist BN52021 （GinkgolideB 5 mg/kg） 0.5 h before and after modeling. The rats in control group received intraperitoneal injection saline （1 mL/ kg）. The animals were killed 1.5, 3, 6, 24, 48, and 72 h after intraperitoneal injection of endotoxin. The pathologic changes of gastric mucosal were observed by hematoxylin-eosin （HE） staining. The content of NO was measured by chemical colorimetry using nitric acid reductase, the ex- pressions of iNOS were measured by imrnuno- histochemistry SP method and the expressions of iNOS mRNA were measured by reverse transcription polymerase chain reaction （RT-PCR）.RESULTS： The pathologic changes of gastric mucosal were significant at 6 h after intraperitoneal injection of endotoxin in LPS group. Erosion, bleeding and necrosis of gastric mucosal were observed. Swollen epithelial cells and developed degeneration were also observed. However, all the above changes were significantly alleviated in prevention group and treatment group. The NO content of gastric mucosa was highest at 6 h after injecting endotoxin in LPS group and the difference was significant between LPS group and control group （84.37 ± 5.44 vs 37.37 ± 1.90, P 〈 0.01）, the difference was significant among PAF antagonist prevention group, treatment group （40.07 ± 3.42, 48.63 ± 3.24） and LPS group （P 〈 0.01）, and the difference was significant among PAF antagonist prevention group, treatment group and control group （P 〈 0.05）. No expr

关 键 词：胃黏膜损伤 内毒素 一氧化氮 诱导型一氧化氮合酶 血小板活化因子 PAF受体拮抗剂 

分 类 号：R573[医药卫生—消化系统]