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目的 :探讨益生菌Faecalibacterium prausnitzii(F.prausnitzii)联合溃克灵防治炎症性肠病的疗效及作用机制。方法 :将50只Sprague-Dawley大鼠随机分为5组:正常组、模型组、F.prausnitzii组、溃克灵组、F.prausnitzii联合溃克灵组。造模前各组灌胃1周(正常组和模型组予生理盐水,其余3组给予相应的F.prausnitzii和溃克灵处理)。采用2,4,6-三硝基苯磺酸(2,4,6-trinitrobenzene sulfonic acid,TNBS)法(80 mg/kg TNBS联合等体积无水乙醇)灌肠复制出结肠炎大鼠模型,3 d后全部处死,观察结肠组织损伤情况,行结肠组织病理学评分;ELISA法测定各组大鼠血浆白介素(interleukin,IL)-10、IL-12、肿瘤坏死因子(tumor necrosis factor,TNF)-α、干扰素(interferon,IFN)-γ水平,计算IL-10/IL-12比值;免疫组化检测肠黏膜IL-10及TNF-α的表达。结果 :F.prausnitzii联合溃克灵组与模型组相比,结肠组织损伤明显改善,组织病理学评分显著降低(P<0.05),血浆IL-10、IL-10/IL-12比值显著升高(P均<0.05),血浆IL-12、IFN-γ显著下降(P<0.05,P<0.001),血浆TNF-α下降但差异无统计学意义,肠黏膜IL-10表达明显升高(P<0.01),肠黏膜TNF-α表达明显降低(P<0.05)。与F.prausnitzii组、溃克灵组相比,F.prausnitzii联合溃克灵组大鼠结肠组织病理学评分降低,IL-10/IL-12比值及血浆IL-10、肠黏膜IL-10表达升高,血浆IL-12、IFN-γ、TNF-α及肠黏膜TNF-α表达下降,但差异无统计学意义。结论:益生菌F.prausnitzii联合中药溃克灵对结肠炎大鼠肠黏膜的预防保护作用,可能与促进外周血及肠黏膜IL-10分泌从而抑制外周血IL-12、TNF-α、IFN-γ产生、降低肠黏膜TNF-α表达等免疫调节机制有关。
Objective: To investigate the efficacy and mechanism of probiotics Faecalibacterium prausnitzii combined with famciclovir in the prevention and treatment of inflammatory bowel disease. Methods: Fifty Sprague-Dawley rats were randomly divided into five groups: normal group, model group, F. prausnitzii group, uracil group, F. prausnitzii combined with uracil group. Before modeling, each group was given gavage for 1 week (normal group and model group were given normal saline, while the other 3 groups were given corresponding F. pulusnitzii and uracil treatment). The rat model of colitis was duplicated by 2,4,6-trinitrobenzene sulfonic acid (TNBS) method (80 mg / kg TNBS with equal volume of absolute ethanol), 3 All rats were sacrificed to observe the injury of colonic tissue and histopathological score of colonic tissue. The levels of interleukin (IL) -10, IL-12, tumor necrosis factor (TNF) α and interferon (IFN) -γ levels were calculated and the ratio of IL-10 / IL-12 was calculated. The expressions of IL-10 and TNF-α in intestinal mucosa were detected by immunohistochemistry. Results: Compared with the model group, F.prausnitzii combined with kuiqiling group had a significant improvement of colonic tissue injury, markedly reduced histopathological score (P <0.05) and a significant increase of plasma IL-10 and IL-10 / IL-12 (P <0.05), while plasma IL-12 and IFN-γdecreased significantly (P <0.05, P <0.001) and plasma TNF-αdecreased but the difference was not statistically significant <0.01). The expression of TNF-α in intestinal mucosa was significantly decreased (P <0.05). Compared with F.prausnitzii group and Kuailingling group, the colon histopathological score, IL-10 / IL-12 ratio and IL-10 in plasma and IL-10 in intestinal mucosa of F.prausnitzii combined with Kuailingling group were decreased But the levels of IL-12, IFN-γ, TNF-α and TNF-α in intestinal mucosa decreased, but the difference was not statistically significant. Conclusion: Preventive and preventive effects of probucol on the intestinal mucosa of colitis rats may be related to the promotion of the secretion of IL-10 in peripheral blood and intestinal mucosa and the inhibition of IL-12, TNF-α and IFN- γ production, reduce intestinal mucosal TNF-α expression and other immune regulatory mechanisms.