清肠栓对三硝基苯磺酸诱导结肠炎大鼠结肠黏膜地址素细胞黏附分子-1表达的影响  

Effect of Qingchang Supporsitory on expression of MAdCAM-1 in the colonic mucosa of rats with TNBS-induced colitis

作　　者：张亚利[1] 唐志鹏[1] 李凯[1] 戴彦成[1] 何新颖[1] 

机构地区：[1]上海中医药大学附属龙华医院消化内科上海中医药大学脾胃病研究所,上海市200032

出　　处：《世界华人消化杂志》2008年第30期3381-3386,共6页World Chinese Journal of Digestology

基　　金：上海市教委重点学科基金资助项目;No.J50305~~

摘　　要：目的:探讨黏膜地址素细胞黏附分子-1(MAdCAM-1)在三硝基苯磺酸(TNBS)诱导大鼠结肠炎发病过程中的作用;研究清肠栓是否通过抑制MAdCAM-1在结肠黏膜的表达,而发挥其抗炎愈疡作用.方法:用TNBS制备实验性大鼠结肠炎模型,大鼠随机分为清肠栓高剂量组、清肠栓低剂量组、柳氮磺胺吡啶组(SASP)、模型Ⅰ组、模型Ⅱ组及正常组.模型Ⅰ组造模3d时,其余5组在给药7d时处死大鼠.取大鼠结肠病变部位标本,进行组织病理学评价,用双抗体夹心酶联免疫吸附法检测结肠组织中LTB4和TNF-α水平,免疫组化染色法和Western blot分析法检测结肠黏膜MAdCAM-1蛋白表达.结果:造模3d时,模型Ⅰ组大鼠结肠黏膜出现明显组织损伤;经过7d处理后,清肠栓组大鼠黏膜组织损伤减轻.模型组结肠黏膜LTB4和TNF-α水平比正常组上升(436.38±66.56,396.81±69.43vs203.76±42.84;394.78±61.53,413.43±47.39vs233.84±55.24,均P<0.01);与模型Ⅱ组比较,各治疗组LTB4和TNF-α水平均下降,尤以清肠栓高剂量组下降明显(275.74±36.35,282.72±47.94,P<0.01).正常组大鼠结肠黏膜固有层MAdCAM-1可见少量表达,模型Ⅰ组大鼠结肠黏膜阳性染色细胞数明显增多;与模型Ⅱ组比较,清肠栓高剂量组、低剂量组和SASP组MAdCAM-1表达均明显下调,尤其在清肠栓高剂量组下调更为显著.结论:清肠栓通过抑制结肠黏膜促炎症因子LTB4和TNF-α释放,以及下调MAdCAM-1表达,而发挥其抗炎愈疡作用.AIM： To investigate the role of mucosal addressin cell adhesion molecule-1 （MAdCAM-1） in the pathogenesis of trinitrobenzene sulfonic acid （TNBS） induced rat colitis and to investigate the mechanisms underlying the anti-inflammatory action of Qingchang Supporistory （QCS）. METHODS： The TNBS induced rat colitis model was established. Rats were randomly divided into QCS high-dose group, QCS low-dose group, sali-cylazosulfapyridine （SASP） group, model Ⅰ group, model Ⅱ group and normal group. Rats in model Ⅰ group were killed at day 3 while other rats were killed after 7 days＇ treatment. Histopathological assessment of the colonic mucosa was performed. LTB4 and TNF-α in the colonic mucosa were determined using sandwich enzyme-linked immunosorbent assay （ELISA）. Expression of MAdCAM-1 was determined using immunohistochemistry staining and Western blot. RESULTS： Three days after TNBS administration, colonic mucosal injury occurred in model I group while colonic mucosal injury was attenuated in QCS group after 7 days＇ treatment of QCS. Compared with normal group, the levels of LTB4 and TNF-α in colonic mucosal were raised in the model group （436.38 ± 66.56, 396.81 ± 69.43 vs 203.76 ± 42.84; 394.78 ± 61.53, 413.43 ± 47.39 vs 233.84 ± 55.24, P 〈 0.01）. Compared with model Ⅱ group, the colonic mucosa levels of LTB4 and TNF-α of all treatment groups were markedly decreased, especially in QCS highdose group （275.74 ± 36.35, 282.72 ± 47.94, both P 〈 0.01）. MAdCAM-1 was constitutively expressed on the lamina propria of normal colonic mucosa and the amount of positive staining cells dramatically were enhanced in model Ⅰ group. Compared with model Ⅱ group, the expression of MAdCAM-1 was significantly down-regulated in QCS high-dose group, QCS low-dose group and SASP group. CONCLUSION： QCS performs significant anti- inflammatory action likely through inhibiting colonic mucosal LTB4 and TNF-α production as well as down-regulating MAdCAM-1 expression.

关 键 词：清肠栓 黏膜地址素细胞黏附分子-1 溃疡性结肠炎 白三烯B4 肿瘤坏死因子-Α 

分 类 号：R285.5[医药卫生—中药学]