二氮杂菲对三硝基苯磺酸所致大鼠结肠炎的治疗作用  

Therapeutic effect of phenanthroline on trinitrobenzene sulfonic acid-induced colitis in rats

作　　者：缪应雷[1] 段丽平[1] 黄华丽[1] 

机构地区：[1]昆明医学院第一附属医院消化科,云南省昆明市650031

出　　处：《世界华人消化杂志》2008年第14期1499-1506,共8页World Chinese Journal of Digestology

基　　金：云南省自然科学基金资助项目;No.2005C0069M~~

摘　　要：目的:研究MMP抑制剂二氮杂菲防治三硝基苯磺酸(trinitrobenzene sulfonic acid,TNBS)肠炎的作用.方法:TNBS建立慢性结肠炎大鼠模型,并将其分为3组:治疗组给药1,10-二氮杂菲;对照组给SASP;空白对照组给予双蒸水1mL.7d后,处死大鼠,测定中性粒细胞髓过氧化物酶(myeloperoxidase,MPO)活性;RT-PCR检测肠道组织MMP-1,MMP-2,MMP-3和TIMP-1mRNA的表达;免疫组织化学方法检测MMP-3和TIMP-1蛋白质的表达.结果:SASP组和二氮杂菲组MPO的A值明显低于对照组(0.25±0.15,0.16±0.09vs0.48±0.34,P=0.025,0.004),MMP-1,MMP-2及MMP-3表达在SASP组(0.19±0.11,0.35±0.21,0.25±0.16)和二氮杂菲组(0.33±0.19,0.29±0.16,0.22±0.17)无明显差异,与对照组(0.45±0.23,0.53±0.17,0.62±0.15)相比明显偏低(P=0.002,0.020,0.000).3组之间TIMP-1mRAN及蛋白表达均无差异.MMP-3在SASP组和二氮杂菲组的蛋白表达量均较对照组低(2971.3±1036.5,2507.7±1101.0vs7812.8±4761.6,P=0.000).结论:二氮杂菲治疗大鼠TNBS肠炎后,肠道损伤积分、MPO以及MMP-1,MMP-2和MMP-3的mRNA的表达均明显下降,但不影响TIMP-1的表达.,AIM： To evaluate the effect of a matrix metalloproteinase （MMP） inhibitor, phenanthroline, on colonic inflammation in experimental colitis induced by trinitrobenzene sulfonic acid （TNBS） in rats. METHODS： A rat model of experimental colitis was induced by administration of TNBS. Animals were divided into 3 groups, treated with 1, 10-phenanthroline （20 mg/kg per day）, sulphasalazine, and double distilled water （1 mL, control group）, respectively. All the animals were killed after 7 days. Myeloperoxidase （MPO） activity was assessed; the mRNA expression of MMP-1, MMP-2, MMP-3 and tissue inhibitor of matrix metalloproteinase-1 （TIMP-1） in colon tissues were detected by semi-quantitative reverse transcription-polymerase chain reaction （RT- PCR）. Meanwhile, MMP-3 and TIMP-1 proteins expression were analyzed by immunohistochemistry. RESULTS： The absorbency value of MPO in the SASP group or phenanthroline group was significantly lower than that in the control group （0.25 ± 0.15, 0.16 ± 0.09 vs 0.48 ± 0.34, P = 0.025, 0.004）. The expression levels of MMP-1, MMP-2 and MMP-3 mRNA had no markedly difference between the SASP group （0.19 ± 0.11, 0.35 ± 0.21, 0.25 ± 0.16） and phenanthroline group （0.33 ±0.19, 0.29 ± 0.16, 0.22 ± 0.17）; however, they were lower than those in the control group （0.45 ± 0.23, 0.53 ± 0.17, 0.62 ± 0.15; P = 0.002, 0.020, 0.000）. There was no significant difference in TIMP-1 mRNA and protein among the three groups. However, the expression of MMP-3 protein in the SASP group or phenanthroline group was lower than that in the control group （2971.3 ± 1036.5, 2507.7 ± 1101.0 vs 7812.8 ± 4761.6, P = 0.000）. CONCLUSION： Phenanthroline may treat TNBS-induced colitis in rats by down-regulating MPO activity and MMP-1, MMP-2 and MMP-3 expression, but it has no effect on TIMP-1 expression.

关 键 词：三硝基苯磺酸 实验性结肠炎 二氮杂菲 基质金属蛋白酶 免疫组织化学 逆转录-聚合酶链反应 

分 类 号：R574.62[医药卫生—消化系统]