双歧杆菌对大鼠溃疡性结肠炎黏膜MMP-2、NF-κB激活的影响

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

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。

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-kB）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-kB 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-kB（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-kB （r=0. 765, P〈0.05）. Conclusion： Bifidobacterium can decrease the expression of MMP-2 by inhibiting the activation of NF-kB in the colonic mucosa of rats with UC. The effect has no significant difference between SASP and Bf group.