谷氨酰胺对非甾体抗炎药所致大鼠小肠黏膜损伤预防作用的研究

Protective effects of glutamine on nonsteroidal anti-inflammatory durg-induced small-intestinal mucosal lesions in rats

目的:研究谷氨酰胺对非甾体抗炎药(NSAID s)所致大鼠小肠黏膜损伤的预防作用,为临床安全用药提供依据。方法:清洁级雄性SD大鼠90只,随机分为9组:4个模型组、4个预防组及1个空白对照组,每组10只。4个模型组分别给予吲哚美辛2.5 mg/kg、阿司匹林50 mg/kg、布洛芬30 mg/kg或塞来昔布20 mg/kg每天2次连续14 d;4个预防组大鼠在给予上述不同NSAID s的同时给予L-谷氨酰胺100 mg/kg,药物均溶于0.5%羧甲基纤维素钠(CMC)2 m l中灌胃;空白对照组大鼠仅给予CMC 2 m。l第15天处死大鼠,采用CM IAS多功能真彩色图像分析系统测量每只大鼠小肠黏膜损伤深度、面积,计算累计损伤深度和累计面积;并应用检测试剂盒测定小肠组织匀浆中髓过氧化物酶(MPO)、丙二醛(MDA)、超氧化物歧化酶(SOD)和一氧化氮(NO)含量。结果:吲哚美辛、阿司匹林、布洛芬及塞来昔布模型组小肠黏膜累计损伤深度分别为5954、511、1361和1447μm,累计损伤面积分别为1 956 592、164 304、339 711和445 611μm2,除阿司匹林组外,其余各组与空白对照组比较差异均有统计学意义(均P<0.05)。吲哚美辛模型组损伤程度重于其他各组(均P<0.05)。吲哚美辛、阿司匹林、布洛芬和塞来昔布预防组小肠黏膜损伤累计深度和面积分别为1206、443、616、723μm和390 450、92 192、209 655、238 827μm2,损伤程度均明显低于对应模型组。吲哚美辛、阿司匹林、布洛芬和塞来昔布各预防组MPO分别为(1.10±0.35)、(0.53±0.19)、(0.83±0.24)和(0.37±0.17)U/g,各对应模型组MPO分别为(2.37±0.63)、(1.66±0.50)、(1.35±0.35)和(1.14±0.38)U/g。各预防组的MPO明显低于各对应模型组,差异有统计学意义,均P<0.05。吲哚美辛预防组MDA明显低于吲哚美辛模型组[(0.50±0.16)比(1.19±0.77)nmol/mg,P<0.05)]。吲哚美辛、阿司匹林、布洛芬和塞来昔布模型组SOD分别为(3.53±0.64)、(4.03±1.28)、(3.44±1.05)和(3.70±1.53)U/mg,均明显低于空白对照组[(5.49±1.09)U/mg,均P<0.05)],各对应预防组SOD分别为(4.03±1.28)、(4.46±1.53)、(4.29±1.10)和(4.00±1.08)U/mg,高于各模型组,但差异无统计学意义。各预防组与各模型组间NO水平差异无统计学意义(P>0.05)。结论:谷氨酰胺对4种NSAID s所致大鼠小肠黏膜损伤具有预防作用。

Objective： To study the protective effects of glutamine on nonsteroidal anti-inflammatory durg（NSAID）-induced small-intestinal mucosal lesions in rats in order to provide the basis for safe drug use.Methods：Ninety SPF grade male Sprague-Dawley rats were randomly allocated into nine groups： the 4 model groups,the 4 protection groups,and the 1 empty control group.Each group comprised ten rats.The rats in the 4 model groups were given indomethacim 2.5 mg/kg,aspirin 50 mg/kg,ibuprofen 30 mg/kg,and celebrex 20 mg/kg twice daily for 14 days,respectively.The rats in the 4 protection groups were given above-mentioned four different kinds of NSAIDs,meanwhile glutamine 100 mg/kg was given at the same time,respectively.All drugs were dissolved in 2 ml of sodium carbaxymethycellulose（CMC）,which was passed into the stomach.The rats in the empty control group were given 2 ml of CMC.On day 15,all rats were sacrificed.The depth and area of rats＇small-intestinal mucosal lesion were measured with the CMIAS multifunction color image analytical system,and the accumulative depth and area of the lesions were calculated.The myeloperoxidase（MPO）,malondialdehyde（MDA）,superoxide dismutase（SOD）,nitric oxide（NO） levels in the small-intestinal homogenate were measured.Results： In the indomethacin,aspirin,ibuprofen,and celebex model groups,the accumulative depth of small-intestinal mucosal lesions was 5 954,511,1 361,and 1 447 μm,respectively,the accumulative area of small-intestinal mucosal lesions was 1 956 592,164 304,339 711,and 445 611 μm2,respectively.The differences were statistically significant in all the model groups compared with the empty control group except the aspirin group（all P0.05）.The severity of lesions in the indomethacin group was greater than that in the other model groups（P0.05）.In the indomethacin,aspirin,ibuprofen,and celebrex protection groups,the acumulative depth and area of small-intestinal mucosal lesion were 1206,443,616,and 723 μm as well as 390 450,92 192,209 655,and 238 827 μm2,respectively.Their severity of lesions was markedly lower than that of the model groups.In the indomethacin,aspirin,ibuprofen,and celebrex protection groups,the MPO levels were（1.10±0.35）,（0.53±0.19）,（0.83±0.24）,and（0.37±0.17）U/g;and in the corresponding model groups,the MPO levels were（2.37±0.63）,（1.66±0.50）,（1.35±0.35）,and（1.14±0.38）U/g.The MPO levels in the protection groups were markedly lower than those in the corresponding model groups.The differences were statistically significant（all P0.05）.The MDA levels in the indomethacin protection group were markedly lower than those in the indomethacin model group[（0.50±0.16）vs（1.19±0.77）nmol/mg,P0.05）].The SOD levels in the indomethacine,aspirin,ibuprofen,and celebrex model groups were respectively（3.53±0.64）,（4.03±1.28）,（3.44±1.05）,and（3.70±1.53）U/mg,which were markedly lower than those in the empty control group[（5.49±1.09）U/mg,all P0.05）].The SOD levels in the corresponding protection groups were respectively（4.03±1.28）,（4.46±1.10）,（4.29±1.53）,and（4.00±1.08）U/mg,which were higher than those in the model groups,but there were no statistically significant differences.There were no statistically significant differences in the NO levels between the protection groups and model groups（P0.05）.Conclusion： Glutamine has protective effects on NSAID-induced small-intestinal mucosal lesions in rats.