Zwolińska-Wcisło Małgorzata, Brzozowski Tomasz, Budak Alicja, Sliwowski Zbigniew, Drozdowicz Danuta, Kwiecień Sławomir, Trojanowska Danuta, Rudnicka-Sosin Lucyna, Mach Tomasz, Konturek Stanisław J, Pawlik Wiesław W, Targosz Aneta
Katedra Fizjologii Klinicznej i Doświadczalnej, Collegium Medicum, Uniwersytetu Jagiellońskiego w Krakowie.
Przegl Lek. 2007;64(3):124-9.
Present-day methods of successful treatment of inflammatory bowel diseases (IBD) result from a better understanding of their pathophysiology due to advances in preclinical studies in this area of knowledge. Until recently microbiological studies have been focused on the bacterial aspects in pathogenesis of GI disorders, however in the last years an interest in the presence of fungi in the gastrointestinal tract has also increased. In this study using an animal model of ulcerative colitis, the impact of fungal colonization of the colon on the intensity of inflammatory changes in the colonic mucosa and the course of their healing was carried out. The macroscopic and microscopic criteria relating to the changes of weight of examined fragments of the colon were evaluated while assessing differences between groups tested. The intensity of intestinal inflammatory changes was determined by assessment of such parameters, as colonic blood flow (CBF), the level of MPO as a marker of colonic neutrophil infiltration intensity and the plasma levels of IL-1beta; and TNF-alpha concentrations. Results at the 3rd day after TNBS rectal administration revealed an increase of weight of isolated segments of inflammed colon, a decrease of CBF and the 4-5 fold increase of plasma MPO activity. Candida colonization of colon mucosa of rats delayed healing of colonic ulcers, induced by TNBS and this was associated with the increased expression of plasma IL-1beta and TNF-alpha levels. Administration of antifungal (fluconazole) or probiotic (Lacidofil) treatment to C. albicans infected rats exerted favorable effect on healing of inflammatory changes in the colon because the area of ulcerations in groups of rats treated with fluconazole or Lacidofil was significantly smaller in comparison with those inoculated with Candida solution only. Administration of fluconazole or Lacidofil significantly decreased the weight of colon segments, the MPO activity and the plasma IL-1beta and TNF-alpha levels, as compared with respective values in the group receiving Candida only. The results of our studies indicate the deteriorating influence of Candida on the healing process of inflamed colon in the animal model of ulcerative colitis. Concomitant therapy with probiotic or antifungal treatment improved healing of colonic lesions, decreased the weight of inflamed colonic tissue and also attenuated the MPO activity and plasma proinflammatory cytokines IL-1beta and TNF-alpha levels.
由于该领域临床前研究的进展,对炎症性肠病(IBD)病理生理学有了更好的理解,从而产生了当今成功治疗炎症性肠病的方法。直到最近,微生物学研究一直集中在胃肠道疾病发病机制的细菌方面,然而在过去几年中,对胃肠道中真菌存在的关注也有所增加。在这项使用溃疡性结肠炎动物模型的研究中,研究了结肠真菌定植对结肠黏膜炎症变化强度及其愈合过程的影响。在评估测试组之间的差异时,评估了与所检查结肠片段重量变化相关的宏观和微观标准。通过评估诸如结肠血流量(CBF)、作为结肠中性粒细胞浸润强度标志物的MPO水平以及血浆IL-1β水平和TNF-α浓度等参数来确定肠道炎症变化的强度。在TNBS直肠给药后第3天的结果显示,炎症结肠分离段的重量增加,CBF降低,血浆MPO活性增加4至5倍。大鼠结肠黏膜的念珠菌定植延迟了由TNBS诱导的结肠溃疡的愈合,这与血浆IL-1β和TNF-α水平的表达增加有关。向感染白色念珠菌的大鼠施用抗真菌(氟康唑)或益生菌(嗜酸乳杆菌)治疗对结肠炎症变化的愈合产生了有利影响,因为与仅接种念珠菌溶液的大鼠组相比,用氟康唑或嗜酸乳杆菌治疗的大鼠组中的溃疡面积明显更小。与仅接受念珠菌的组中的相应值相比,施用氟康唑或嗜酸乳杆菌显著降低了结肠段的重量、MPO活性以及血浆IL-1β和TNF-α水平。我们的研究结果表明,在溃疡性结肠炎动物模型中,念珠菌对炎症结肠的愈合过程有恶化影响。益生菌或抗真菌治疗的联合疗法改善了结肠病变的愈合,减轻了炎症结肠组织的重量,还减弱了MPO活性以及血浆促炎细胞因子IL-1β和TNF-α水平。