双歧杆菌对大鼠溃疡性结肠炎黏膜MMP-2、NF-κB激活的影响

目的:观察双歧杆菌(Bf)活制剂对大鼠溃疡性结肠炎(UC)发生、发展的影响,并检测其对细胞核因子(NF-κB)、基质金属蛋白酶-2(MMP-2)表达影响,探讨双歧杆菌的发病机制。方法:将40只SPF级SD雄性大鼠随机分为4组:空白对照组、模型组、柳氮磺胺吡啶(SASP)组、双歧杆菌(Bf)组。用2,4,6-三硝基苯磺酸(2,4,6-TNBS)和10%乙醇混溶(1∶1,V/V)灌肠建立大鼠UC模型;双歧杆菌(Bf)给大鼠灌服双歧杆菌活菌制剂;柳氮磺胺吡啶组则给大鼠灌服柳氮磺胺吡啶(SASP),空白对照组及模型组则正常饲养,不予任何处理,共4周。4周后处死全部大鼠,观察大鼠一般情况的变化(毛色、精神、活动、食欲、睡眠、体力、大便情况),应用免疫组化SP法检测应用Bf前后NF-κB、MMP-2变化。结果:与空白对照组相比,应用双歧杆菌制剂后,UC的症状、组织损害均较模型组明显减轻。同时MMP-2表达较模型组降低(SASP:3.200±0.761;Bf:4.270±1.600,P<0.05),NF-κB的表达也降低(SASP:3.520±1.029;Bf:3.400±1.037,P<0.05),但较正常对照组仍有明显增加;MMP-2的表达与NF-κB的表达呈显著的正相关(r=0.765,P<0.05)。同时,SASP组与Bf组无显著差别(P<0.05)。结论:生态制剂Bf对UC有治疗作用,可能是通过抑制NF-κB的核结合活性,进而降低MMP-2的表达完成的,其作用与SASP作用相当,可作为临床上治疗药物之一。

Effect of Bifidobacterium on the Expression of Matrix Metalloproteinase-2 and Nuclear Factor-kappa B in Rat Intestinal Mucosa with Ulcerative Colitis

Objective: To investigate the effects of Bifidobacterium(Bf) on the expression of matrix metalloproteinase-2(MMP-2) and activation of nuclear factor-kappa B(NF-κB)in the intestional mucosa with ulcerative colitis(UC).Methods: UC was induced by 2,4,6-triintrobenzene sulfonic acid(2,4,6-TNBS) and 10% alcohol(1∶1,V/V).All rats were divided in random into four groups as following: normal group,model control group,Bf group and SASP group.After one month,the rats were killed for assaying the MMP-2 and NF-κB with immunohistochemical staining.Results: Both symptoms and the lesions of colonic mucosa were slighter in the animals treated with Bifidobacterium and SASP than those of model control(P<0.05).And compared with those of the model control group,the expression of MMP-2(SASP: 3.200±0.761,Bf:(4.270)±1.600,P<0.05) and NF-κB(SASP:3.520±1.029,Bf:3.400±1.037,P<0.05)in Bf group and SASP group were significantly decreased(P<0.05), but both were higher than in normal group(both P<0.05).MMP-2 activation has significant positive correlation with the NF-κB(r=(0.765,) P<(0.05).) Conclusion: Bifidobacterium can decrease the expression of MMP-2 by inhibiting the activation of NF-κB in the colonic mucosa of rats with UC.The effect has no significant difference between SASP and Bf group.