CAJ | 학술논문

目的利用短期口服小剂量双氯芬酸建立大鼠非甾体类抗炎药(NSAID)小肠黏膜损伤模型,观察甲硝唑、雷贝拉唑对NSAID所致小肠黏膜损伤的预防作用.方法将64只大鼠随机抽签分为空白组、模型组、甲硝唑组和雷贝拉唑组,每组16只.再将各组动物进一步分为T1(急性期)和T2(亚急性期)亚组,每组8只.甲硝唑组和雷贝拉唑组大鼠在造模前1 d分别给予甲硝唑50 mg/kg或雷贝拉唑15 mg/kg灌胃1次.次日,空白组以1 ml蒸馏水灌胃每天2次;模型组给予双氯芬酸7.5 mg/kg每天2次;甲硝唑组给予双氯芬酸7.5 mg/kg和甲硝唑50 mg/kg,每天2次;雷贝拉唑组给予双氯芬酸7.5 mg/kg和雷贝拉唑15 mg/kg,每天2次.各组的T1亚组灌胃1 d后处死,T2亚组灌胃5 d后处死.结果小剂量双氯芬酸能引起小肠黏膜显著出血性损伤,小肠黏膜可见大量红斑、糜烂、溃疡,局部肠腔可见囊样扩张.模型组的T1、T2亚组损伤均较空白组严重(P＜0.05),且T2组损伤明显大于T1组(P＜0.05).甲硝唑和雷贝拉唑组的T1,T2亚组的损伤均小于模型组(均P＜0.05).模型组T1亚组的血清一氧化氮含量明显低于空白组(P＜0.05),T2亚组则明显高于空白组(P＜0.05).模型组与甲硝唑组、雷贝拉唑组之间一氧化氮含量比较差异无统计学意义(P＞0.05).结论短期小剂量口服双氯芬酸后,即可引起小肠黏膜损伤.并随时间呈进行性加重; 血清一氧化氮含量在小肠黏膜损伤后呈现先降低,后升高趋势.甲硝唑、雷贝拉唑对NSAID诱发的小肠黏膜损伤具有一定的预防作用.
목적 이용단기구복소제량쌍록분산건립대서비치체류항염약(NSAID)소장점막손상모형,관찰갑초서、뢰패랍서대NSAID소치소장점막손상적예방작용.방법 장64지대서수궤추첨분위공백조、모형조、갑초서조화뢰패랍서조,매조16지.재장각조동물진일보분위T1(급성기)화T2(아급성기)아조,매조8지.갑초서조화뢰패랍서조대서재조모전1 d분별급여갑초서50 mg/kg혹뢰패랍서15 mg/kg관위1차.차일,공백조이1 ml증류수관위매천2차;모형조급여쌍록분산7.5 mg/kg매천2차;갑초서조급여쌍록분산7.5 mg/kg화갑초서50 mg/kg,매천2차;뢰패랍서조급여쌍록분산7.5 mg/kg화뢰패랍서15 mg/kg,매천2차.각조적T1아조관위1 d후처사,T2아조관위5 d후처사.결과 소제량쌍록분산능인기소장점막현저출혈성손상,소장점막가견대량홍반、미란、궤양,국부장강가견낭양확장.모형조적T1、T2아조손상균교공백조엄중(P＜0.05),차T2조손상명현대우T1조(P＜0.05).갑초서화뢰패랍서조적T1,T2아조적손상균소우모형조(균P＜0.05).모형조T1아조적혈청일양화담함량명현저우공백조(P＜0.05),T2아조칙명현고우공백조(P＜0.05).모형조여갑초서조、뢰패랍서조지간일양화담함량비교차이무통계학의의(P＞0.05).결론 단기소제량구복쌍록분산후,즉가인기소장점막손상.병수시간정진행성가중; 혈청일양화담함량재소장점막손상후정현선강저,후승고추세.갑초서、뢰패랍서대NSAID유발적소장점막손상구유일정적예방작용.
Objective To establish rat model of small intestinal damage by administrating low dose of diclofenac in short-term and to observe the preventive effect on non steroidal anti-inflammatory drugs (NSAIDs) induced small intestinal damage by metronidazole and rabeprazole.Methods Sixty-four rats were randomly divided into control,model,metronidazole and rabeprazole groups with 16 each.The rats in four groups were then further separated into acute stage (T1) and subacute stage (T2) groups.The rats were lavaged with metronidazole (50 mg/kg) and rabeprazole (15 mg/kg) before modeling.The rats in control,model,metronidazole and rabeprazole groups were lavaged with 1ml of distilled water, 7.5 mg/kg diclofenac,50 mg/kg of metronidazole plus 7.5mg/kg of diclofenac,15 mg/kg of rabeprazole plus 7.5mg/kg of diclofenac twice a day,respectively.The rats in T1 group were sacrificed on day 1 and T2 group on day 5.Results Administration of diclofenac induced multiple lesions in the small intestine, such as obviously erythema,erosion,ulcer and cystoid expansion.The lesions in T2 of model group was more seriously than that in T1 group(P＜0.05).And the lesions in model group was also more seriously than that in metronidazole and rabeprazole groups (both T1 and T2 groups,P < 0.05).Serum concentration of NO in T1 of model group was obviously lower than that in control group (P＜0.05),but it was higher in T2 of model group compare to the control group (P＜0.05).There were no significant difference among metronidazole,rabeprazole and model groups in serum level of NO (P>0.05). Conclusions The lesions of small intestinal can be induced by administration of diclofenac.The serum level of NO presents a tendency with decrease before increase afterwards.The metronidazole or rabeprazole has preventive effect on small intestinal lesions.