Alberta Institute for Human Nutrition, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
J Pediatr Gastroenterol Nutr. 2010 Mar;50(3):321-8. doi: 10.1097/MPG.0b013e3181ae2ba0.
Intestinal permeability and barrier function are regulated by expression of tight junction proteins. Lipopolysaccharide (LPS), tumor necrosis factor-alpha, and interleukin-1beta induce expression of nitric oxide (NO) and reduce the expression of gut tight junction proteins. The purpose of this study was to determine whether dietary gangliosides (GGs) increase the concentration of the anti-inflammatory cytokine interleukin-10 (IL-10) in response to LPS, thereby inhibiting NO production and protecting gut occludin tight junction protein from degradation.
Rats were fed semipurified diets with (n = 16) or without (n = 16) GGs (0.1% w/w of total lipid). After 2 weeks of feeding, animals were injected with saline (n = 8/diet group) or LPS (n = 8/diet group) (IP, 3 mg mL(-1) kg(-1)). Intestinal tissue, mucosa, and blood sample were collected 6 hours post-LPS exposure. The effect of dietary GGs on production/expression of IL-10, NO, inducible NO synthase, and occludin protein was determined.
Dietary GGs increased IL-10 content in intestinal mucosa significantly by 32-fold (P < 0.0001) and in plasma by 2.4-fold (P < 0.001). Feeding animals a ganglioside-enriched diet decreased total NO content in intestinal mucosa and plasma by 44% and 30%, respectively, and inhibited inducible NO synthase expression following LPS exposure compared with control animals. Dietary GGs reduced the degradation of occludin tight junction protein in response to LPS.
Dietary GGs inhibit degradation of gut occludin tight junction protein during LPS-induced acute inflammation. Thus, dietary GGs have a role in protecting the integrity of the intestinal barrier during acute gut inflammation.
肠道通透性和屏障功能受紧密连接蛋白的表达调控。脂多糖（LPS）、肿瘤坏死因子-α和白细胞介素-1β诱导一氧化氮（NO）的表达，并减少肠道紧密连接蛋白的表达。本研究旨在确定饮食神经节苷脂（GGs）是否会增加抗炎细胞因子白细胞介素-10（IL-10）的浓度，从而抑制 NO 的产生并防止肠道闭合蛋白紧密连接蛋白降解。
大鼠分别用（n=16）或不用（n=16）GGs（总脂质的 0.1%w/w）喂养半纯化饮食。喂养两周后，动物用生理盐水（n=8/饮食组）或 LPS（n=8/饮食组）（IP，3mg mL-1kg-1）注射。LPS 暴露后 6 小时采集肠道组织、黏膜和血液样本。确定饮食 GGs 对 IL-10、NO、诱导型一氧化氮合酶和闭合蛋白的产生/表达的影响。
饮食 GGs 使肠黏膜中 IL-10 的含量显著增加了 32 倍（P<0.0001），血浆中增加了 2.4 倍（P<0.001）。用富含神经节苷脂的饮食喂养动物，使肠黏膜和血浆中的总 NO 含量分别降低了 44%和 30%，并抑制了 LPS 暴露后诱导型一氧化氮合酶的表达。饮食 GGs 减少了 LPS 诱导的紧密连接蛋白 occludin 的降解。
饮食 GGs 抑制 LPS 诱导的急性炎症期间肠道 occludin 紧密连接蛋白的降解。因此，饮食 GGs 在急性肠道炎症期间对保护肠道屏障的完整性具有作用。
