塞来昔布对大鼠溃疡性结肠炎的作用

The role of celecoxib on rats with ulceractive colitis

目的观察塞来昔布对三硝基苯磺酸(TNBS)灌肠诱发结肠炎的大鼠的血清前列腺素E2(prostagland E2,PGE2)及结肠组织COX-2水平影响,并探讨塞来昔布对溃疡性结肠炎(ulcerative colitis,UC)的作用及作用机制。方法 Wistar雄性大鼠40只,随机分成4组,每组10只,A组为正常对照组(未经任何处理)、B组为水杨酸偶氮磺胺吡啶(salicylazosulfapyridine,SASP)组、C组为塞来昔布组、D组为模型对照组(0.9%氯化钠注射液)。B、C、D三组均采用TNBS/乙醇灌肠制作大鼠UC模型后,B组SASP 200 mg/kg、C组塞来昔布10 mg/kg、D组0.9%氯化钠注射液1 ml每天灌胃给药1次,连续治疗7 d后处死所有存活大鼠。在造模成功后每天评定各组大鼠一般状况、DAI(disease activity index)评分;药物治疗后第7天在全麻下心脏采血,采用酶联免疫吸附法(ELISA)检测血清PGE2浓度,取病变组织行HE染色和COX-2免疫组织化学染色。结果 B组和C组一般情况及消化道症状好于D组。C组DAI评分高于B组(P<0.01),与D组相接近(P=0.418),无显著性差异。A组(75.28±7.55)血清PGE2含量表达量均明显少于其他三组(P<0.05)。C组血清PGE2含量表达少于B组、D组(P<0.01)。结论塞来昔布对TNBS诱导的UC无明显治疗作用。虽然塞来昔布可以使TNBS诱发的肠炎大鼠结肠病变处的炎症减轻,使血清PGE2等炎症相关因子表达减少,但未能明显减轻UC肠黏膜的损害,甚至有加重疾病症状的倾向,因此,塞来昔布能否用于UC的治疗仍然有待进一步研究。

Objective To investigate the effects of celecoxib on rats with 2, 4, 6-trinitrobenzenesulphonic acid （TN- BS）- induced colitis in order to understand its underlying mechanisms in treatment of IBD. Methods 30 male Wistar rats were given 2, 4, 6-trinitrobenzenesulphonic acid-induced colitis and were randomly divided into three groups, SASP （200 mg/kg） treated group （group B） and eelecoxib （10 mg/kg） treated group （group C）, 0.9% sodium chloride group （group D） with 10 each, another 10 rats were severed as normal control （group A）. Except the rats in normal control group, all rats were intragastric administrated and were killed 7-day after colitis treatment and assessed with fol lowing variables including pathological change with HE staining of colon; the serum level of PGE2 was detected by enz ymelinkde immunosorbent assay （ELISA） , respectively. And the COX-2 was measured by immunohistochemistry. Re sults The DAI in group B, C and D increased since TNBS was administered rectally, but in group C, which was signif icantly higher than that in group B （ P 〈 0.01 ）, and was similar to that in the group D （ P = 0. 418 ） ; the serum level of PGE2 in group A （75.28_7.55） was significantly lower than that in group B, C and D （P〈0.05）. But in group C, which was significantly lower than that in group B and D （P 〈 0.01 ）. Conclusion Celecoxib has no obvious therapeu tic effect on TNBS induced ulcers colitis. The celecoxib can reduce the inflammation of colon tissues of experimental co litis induced by TNBS, and decrease expression of the serum PGE2 , but even have the tendency of severity of the dis- ease symptoms. Therefore, whether celecoxib can be used in the treatment of ulcerative colitis or not remains to be fur ther researched.