4-氨基水杨酸对三硝基苯磺酸诱导的大鼠结肠炎模型的影响

Effect of 4-aminosalicylic acid on trinitrobenzene sulfonic acid-induced colitis in rats

目的:观察4-氨基水杨酸(4-ASA)治疗三硝基苯磺酸(TNBS)诱导结肠炎的疗效并探讨其作用机制.方法:直肠给予雌性SD大鼠TNBS诱导结肠炎,应用4-ASA-Na(100,200mg/kg)对其进行治疗,并以5-氨基水杨酸(5-ASA)作为阳性对照,分别于1wk及2wk后取结肠标本评价炎症程度及指标检测,结肠炎症的评价包括大体形态损伤、组织学变化和髓过氧化物酶(MPO)活性,生化法检测超氧化物歧化酶(SOD)活性、丙二醛(MDA)水平,逆转录-多聚酶链反应(RT-PCR)检测结肠组织白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-αmRNA表达水平.结果:与模型组比较,4-ASA低剂量组和高剂量组的大体和组织学评分均降低(P均<0.05),MPO活性降低(P<0.05),SOD活性升高(P<0.05),MDA水平降低(P<0.05),IL-1β和TNF-α水平降低(P均<0.05).与5-ASA组相比,其疗效无显著性差异.结论:4-ASA对TN-BS诱导的大鼠结肠炎具有良好的疗效,其具有抗氧化作用,可减少IL-1β和TNF-α的生成,从而减轻症状和结肠炎性损伤.

AIM： To investigate the effect of 4-aminosalicylic acid （4-ASA） on trinitrobenzene sulfonic acid （TNBS） -induced colitis in rats and to clarify the related mechanism. METHODS： Colitis was induced in female SD rats by rectal administration of TNBS resolved in ethanol. The colitis rats were treated with 4- ASA-Na with doses of 100 and 200 mg/kg respectively for 2 weeks. 5-aminosalicylic acid （5-ASA） and normal saline were used as control groups. The colonic inflammation including macroscopic and histological changes and myeloperoxidase （MPO） activity was evaluated. Superoxide dismutase （SOD） activity and malondialdehyde （MDA） level in colonic mucosa were detected by biochemical methods. The expressions of interleukin-1β （ IL-1β） and tumor necrosis factor-or （TNF-α） mRNAs in colonic mucosa were determined by a reverse transcription polymerase chain reaction （RT-PCR） method. RESULTS： Compared with TNBS control group, the macroscopic and histological scores and MPO activity in 4-ASA treated groups were decreased （ P 〈 0.05 ）, SOD activity was increased （ P 〈 0.05 ）, and the level of MDA in colonic mucosa was reduced significantly （P 〈 0. 05 ）. The expressions of IL-1β and TNF-α mRNAs in colonic mucosa were also decreased significantly （ P 〈 0.05 ）. The intracolonic administration with 4-ASA had no more therapeutic effect than topical treatment with 5-ASA. CONCLUSION： The topical treatment with 4-ASA can significantly attenuate the colonic damage in TNBS-induced colitis in rats and it may be related to the antioxidant mechanism and the inhibition of the expression of proinflammatory cytokines including IL-1β and TNF-α.