Abstract:

Ulcerative colitis （UC） is a chronic， nonspecific inflammatory disease occurring in the rectum and colon， and its incidence has increased significantly in recent years. This study aimed to explore the improvement effect of recombinant human lactoferrin and recombinant human lysozyme derived from genetically modified cow milk on UC， mice UC models were established by dextran sodium sulfate （DSS）. 30 male C57BL/6N mice were randomly divided into blank control group （CON group）， model control group （DSS group）， low-concentration lactoferrin group （L-rLF group， 50 mg·kg^-1·BW^-1）， high-concentration lactoferrin group （H-rLF， 100 mg·kg^-1·BW^-1）， low-concentration lysozyme group （L-rLZM group， 50 mg·kg^-1·BW^-1） and high-concentration lysozyme group （H-rLZM group， 100 mg·kg^-1·BW^-1）. After model building， the mice were given lactoferrin and lysozyme by gavage for one week. The serum and colon of mice were collected to observe the pathological changes of organs， and inflammatory factors and intestinal flora were determined. The results showed that， compared with the model group， disease activity index （DAI）， colon length reduction and histopathological score of mice in the low-concentration lactoferrin group and low-concentration lysozyme group were significantly reduced after lactoferrin and lysozyme gavage. The expression of prionflammatory factors （IL-6， LL-1β， TNF-α） in colon tissue and the concentration of lipopolysaccharide （LPS） in serum and liver were significantly decreased， and the structure of intestinal microflora was also significantly improved in the high-concentration lactoferrin group. The results showed that both recombinant lactoferrin and recombinant lysozyme could improve the ulcerative colitis in mice to varying degrees. This study provided a new idea and theoretical support for the future application of recombinant human lactoferrin and recombinant human lysozyme.

Key words: ulcerative colitis, recombinant human lactoferrin, recombinant human lysozyme, inflammatory cytokines, intestinal flora

摘要：

溃疡性结肠炎（ulcerative colitis，UC）是一种发生于直肠和结肠的慢性非特异性炎症疾病，近年来发病率明显上升。为探究转基因牛乳中提取的重组人乳铁蛋白和重组人溶菌酶对改善UC的作用，采用葡聚糖硫酸钠（dextran sulfate sodium salt，DSS）构建小鼠UC模型，30只雄性C57BL/6N小鼠随机分为空白对照组（CON组）、模型对照组（DSS组）、低浓度乳铁蛋白组（L-rLF组，50 mg·kg^-1·BW^-1）、高浓度乳铁蛋白组（H-rLF组，100 mg·kg^-1·BW^-1）、低浓度溶菌酶组（L-rLZM组，50 mg·kg^-1·BW^-1）和高浓度溶菌酶组（H-rLZM组，100 mg·kg^-1·BW^-1）。造模后用重组乳铁蛋白和溶菌酶分别灌胃1周，取小鼠血清及结肠，观察器官病理变化，测定炎症因子以及肠道菌群等相关指标。研究结果显示，与模型组相比，低浓度乳铁蛋白组和低浓度溶菌酶组小鼠疾病活动指数（disease activity index，DAI）、结肠缩短量、组织病理学评分均显著降低，且结肠组织中促炎因子（IL-6、lL-1β、TNF-α）表达量、血清和肝脏中脂多糖（lipopolysaccharide，LPS）浓度显著降低，高浓度乳铁蛋白处理组小鼠肠道菌群结构显著改善。表明重组人乳铁蛋白和重组人溶菌酶均可以不同程度地改善小鼠UC，为重组人乳铁蛋白和重组人溶菌酶的未来应用提供了新的思路和理论支持。

关键词: 溃疡性结肠炎, 重组人乳铁蛋白, 重组人溶菌酶, 炎症因子, 肠道菌群