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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 preventive effect of glutamine on intestinal mucosal lesion in rats induced by non-steroidal anti-inflammatory drugs (NSAIDs), and to provide basis for clinical safe medication. Methods: Ninety clean male SD rats were randomly divided into 9 groups: 4 model groups, 4 prevention groups and 1 blank control group, with 10 rats in each group. The four model groups were given indomethacin 2.5 mg / kg, aspirin 50 mg / kg, ibuprofen 30 mg / kg or celecoxib 20 mg / kg twice daily for 14 days. The rats in the four prevention groups The same NSAID s were administered simultaneously with 100 mg / kg of L-glutamine. The drugs were dissolved in 2 ml of 0.5% sodium carboxymethylcellulose (CMC). The rats in the blank control group were given only CMC 2 m . The rats were sacrificed on the 15th day, the intestinal mucosal lesion depth and area of each rat were measured by CM IAS multifunctional true color image analysis system, and the cumulative damage depth and cumulative area were calculated. The detection kit was used to determine the medullary Peroxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) were detected. Results: The cumulative damage of intestinal mucosa in indomethacin, aspirin, ibuprofen and celecoxib groups were 5954, 511, 1361 and 1447 μm, respectively, and the cumulative damage area was 1 956 592, 164 304, 3339 711 and 445, respectively 611μm2, with the exception of aspirin group, the remaining groups and the blank control group differences were statistically significant (P <0.05). Indomethacin model group was more damaged than other groups (all P <0.05). Indomethacin, aspirin, ibuprofen and celecoxib prevention group intestinal mucosal damage cumulative depth and area were 1206,443,616,723μm and 390 450,92 192,209 655,238 827μm2, the degree of injury were significantly Lower than the corresponding model group. (1.10 ± 0.35), (0.53 ± 0.19), (0.83 ± 0.24) and (0.37 ± 0.17) U / g for indomethacin, aspirin, ibuprofen and celecoxib, The MPO of model group were (2.37 ± 0.63), (1.66 ± 0.50), (1.35 ± 0.35) and (1.14 ± 0.38) U / g, respectively. The MPO of each prevention group was significantly lower than that of the corresponding model group, the difference was statistically significant (P <0.05). MDA in indomethacin group was significantly lower than that in indomethacin group [(0.50 ± 0.16) vs (1.19 ± 0.77) nmol / mg, P <0.05). The SOD of indomethacin, aspirin, ibuprofen and celecoxib group were (3.53 ± 0.64), (4.03 ± 1.28), (3.44 ± 1.05) and (3.70 ± 1.53) U / mg respectively (4.03 ± 1.28), (4.46 ± 1.53), (4.29 ± 1.10) and (4.00 ± 1.08) in the blank control group [(5.49 ± 1.09) U / mg, all P < ) U / mg, higher than the model group, but the difference was not statistically significant. There was no significant difference in NO level between prevention group and each model group (P> 0.05). CONCLUSION: Glutamine can prevent the intestinal mucosal lesion in four NSAIDs-induced rats.