细胞色素P450 4B1（CYP4B1）信使核糖核酸（mRNA）水平升高与咖啡酸对葡聚糖硫酸钠诱导的小鼠结肠炎的抑制作用有关。
Increased CYP4B1 mRNA is associated with the inhibition of dextran sulfate sodium-induced colitis by caffeic acid in mice.
作者信息
Ye Zhong, Liu Zhiping, Henderson Abigail, Lee Kwangwon, Hostetter Jesse, Wannemuehler Michael, Hendrich Suzanne
机构信息
The Iowa State University, Department of Food Science and Human Nutrition, 224D MacKay, Ames, IA 50011, USA.
出版信息
Exp Biol Med (Maywood). 2009 Jun;234(6):605-16. doi: 10.3181/0901-RM-1. Epub 2009 Mar 23.
Susceptibility to inflammatory bowel diseases depends upon interactions between the genetics of the individual and induction of chronic mucosal inflammation. We hypothesized that administration of dietary phenolics, caffeic acid and rutin, would suppress upregulation of inflammatory markers and intestinal damage in a mouse model of colitis. Colitis was induced in C3H/ HeOuJ mice (8 weeks old, 6 male/6 female per treatment) with 1.25% dextran sulfate sodium (DSS) for 6 d in their drinking water. Rutin (1.0 mmol (524 mg)/kg in diet), caffeic acid (1.0 mmol (179 mg)/kg in diet), and hypoxoside extract (15 mg/d, an anticolitic phenolic control) were fed to the mice for 7 d before and during DSS treatment, as well as without DSS treatment. Body weight loss was prevented by rutin and caffeic acid during DSS treatment. Colon lengths in mice fed caffeic acid and hypoxoside during DSS treatment were similar to DSS-negative control. Food intake was improved and myeloperoxidase (MPO) was decreased with each phenolic treatment in DSS-treated mice compared with DSS treatment alone. Colonic mRNA expression of IL-17 and iNOS were inhibited when IL-4 was increased by each phenolic treatment combined with DSS, whereas CYP4B1 mRNA was increased only by caffeic acid in DSS-treated mice, compared with DSS treatment alone. Colonic and cecal histopathology scores of DSS-treated mice were significantly more severe (P < 0.01) than in mice fed caffeic acid before and during DSS treatment, based on mucosal height, necrosis, edema, erosion, and inflammatory cell infiltration. Although both rutin and caffeic acid suppressed the expression of selected inflammatory markers, only caffeic acid protected against DSS-induced colitis, in association with normalization of CYP4B1 expression. The inhibition of DSS-induced colitic pathology by caffeic acid was mediated by mechanisms in addition to anti-inflammatory effects that deserve further study.
炎症性肠病的易感性取决于个体基因与慢性黏膜炎症诱导之间的相互作用。我们推测，给予膳食酚类物质、咖啡酸和芦丁，会抑制结肠炎小鼠模型中炎症标志物的上调和肠道损伤。用1.25%硫酸葡聚糖钠（DSS）在C3H/HeOuJ小鼠（8周龄，每组治疗6只雄性/6只雌性）饮用水中诱导结肠炎6天。在DSS处理前和处理期间以及未进行DSS处理时，给小鼠喂食芦丁（饮食中1.0 mmol（524 mg）/kg）、咖啡酸（饮食中1.0 mmol（179 mg）/kg）和次黄苷提取物（15 mg/d，一种抗结肠炎酚类对照物）。在DSS处理期间，芦丁和咖啡酸可防止体重减轻。在DSS处理期间，喂食咖啡酸和次黄苷的小鼠结肠长度与DSS阴性对照相似。与单独的DSS处理相比，每种酚类处理的DSS处理小鼠的食物摄入量有所改善，髓过氧化物酶（MPO）降低。当每种酚类处理与DSS联合增加IL-4时，IL-17和诱导型一氧化氮合酶（iNOS）的结肠mRNA表达受到抑制，而与单独的DSS处理相比，仅咖啡酸可增加DSS处理小鼠的CYP4B1 mRNA。基于黏膜高度、坏死、水肿、糜烂和炎症细胞浸润，DSS处理小鼠的结肠和盲肠组织病理学评分明显比在DSS处理前和处理期间喂食咖啡酸的小鼠更严重（P < 0.01）。尽管芦丁和咖啡酸均抑制了选定炎症标志物的表达，但只有咖啡酸与CYP4B1表达正常化相关，可预防DSS诱导的结肠炎。咖啡酸对DSS诱导的结肠病理的抑制作用是由除抗炎作用之外的机制介导的，值得进一步研究。
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