Wapnir Raul A, Sherry Barbara, Codipilly Champa N, Goodwin Leslie O, Vancurova Ivana
The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY 11030, USA.
Dig Dis Sci. 2008 Jan;53(1):80-7. doi: 10.1007/s10620-007-9826-0. Epub 2007 May 8.
The objective of this study was to test the hypothesis that in an animal model of cathartic-induce intestinal dysfunction the proabsorptive effects of gum arabic (GA) could be associated with modulation of nuclear factor-kappaB (NF-kappaB) and with reduction of the inflammatory response caused by cathartics, as evidenced by intestinal mucosa cytokine production and gene expression. Juvenile male rats were given a phenolphthalein-magnesium citrate solution for 6 days, by itself or supplemented with either 10 or 20 g L(-1) GA, as a sole source of fluid. The controls given were tap water alone or with added 20 g L(-1) GA. The animals were euthanized and small-intestinal mucosa nuclear fractions and RNA were isolated. NF-kappaB p65 activity was highest after administration of cathartics, lowest in controls, and intermediate in GA-treated rats. Mucosal IL-1beta was overexpressed in tissues from cathartic-treated rats and from rats given high-GA solutions. Gene-array analysis revealed a complex pattern of gene regulation by cathartics which selectively upregulated several subfamilies of cytochrome P-450 family 2 genes. Co-administration of GA did not block this effect. These findings suggest that local anti-inflammatory effects on the small intestine could be obtained by administration of a nonabsorbable proteoglycan such as GA.
在泻剂诱导的肠道功能障碍动物模型中,阿拉伯胶(GA)的促吸收作用可能与核因子-κB(NF-κB)的调节以及泻剂引起的炎症反应的减轻有关,这可通过肠黏膜细胞因子产生和基因表达得到证明。将幼年雄性大鼠给予酚酞-枸橼酸镁溶液6天,单独给予或补充10或20 g L⁻¹ GA,作为唯一的液体来源。给予的对照是单独的自来水或添加20 g L⁻¹ GA的自来水。对动物实施安乐死后,分离小肠黏膜核组分和RNA。NF-κB p65活性在给予泻剂后最高,在对照组中最低,在GA处理的大鼠中处于中间水平。黏膜白细胞介素-1β在接受泻剂处理的大鼠和给予高GA溶液的大鼠的组织中过度表达。基因阵列分析揭示了泻剂对基因调节的复杂模式,其选择性地上调了细胞色素P-450家族2基因的几个亚家族。GA的共同给药并未阻断这种作用。这些发现表明,通过给予不可吸收的蛋白聚糖如GA,可以对小肠产生局部抗炎作用。