Park Eek Joong, Suh Miyoung, Thomson Benjamin, Ma David W L, Ramanujam Kalathur, Thomson Alan B R, Clandinin Michael Tom
Nutrition and Metabolism Research Group, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
Shock. 2007 Jul;28(1):112-7. doi: 10.1097/SHK.0b013e3180310fec.
Our previous study demonstrated that feeding ganglioside increased total ganglioside content while decreasing cholesterol and caveolin-1 content in developing rat intestinal lipid microdomains. Cholesterol or caveolin depletion in membranes inhibits inflammatory signaling by disrupting microdomain structure. We hypothesized that dietary ganglioside-induced reduction in cholesterol content will reduce proinflammatory mediators in the intestinal mucosa after acute exposure to bacterial endotoxin. Weanling rats were fed semipurified diets with 0.1% (wt/wt of total fat) gangliosides (treatment) or without ganglioside (control). After 2 weeks of feeding, half of animals from each diet group were injected with saline or lipopolysaccharide (LPS) endotoxin (Escherichia coli serotype O111:B4, intraperitoneal, 3 mg/kg body weight) to induce acute gut inflammation. Intestinal mucosa and blood were collected after 6 h. The effect of dietary ganglioside on proinflammatory mediators including cholesterol, platelet-activating factor, prostaglandin E2, leukotriene B4 (LTB4), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) was determined in inflamed mucosa and blood. Feeding animals the control diet increased cholesterol content in intestinal lipid microdomains by 92% after LPS injection compared with saline injection. Animals fed the ganglioside diet significantly decreased cholesterol content in lipid microdomains by 60% compared with animals fed the control diet. Feeding animals the ganglioside diet increased total ganglioside content by 90% while decreasing platelet-activating factor content by 45% in the inflamed mucosa by acute systemic exposure to LPS compared with animals fed the control diet. When animals were fed the ganglioside diet, the levels of prostaglandin E2, LTB4, IL-1beta, and TNF-alpha were lower in inflamed mucosa, and LTB4, IL-1beta, and TNF-alpha were decreased in plasma by 41%, 58%, and 55% compared with control animals, respectively. The present study demonstrates that dietary gangliosides inhibit proinflammatory signals in the intestine and blood induced by acute inflammation of LPS and suggests therapeutic potential in the treatment and management of acute local and systemic inflammatory diseases.
我们之前的研究表明，在发育中的大鼠肠道脂质微区中，喂食神经节苷脂可增加总神经节苷脂含量，同时降低胆固醇和小窝蛋白-1含量。膜中胆固醇或小窝蛋白的耗竭会通过破坏微区结构来抑制炎症信号传导。我们假设，急性暴露于细菌内毒素后，饮食中的神经节苷脂导致的胆固醇含量降低将减少肠黏膜中的促炎介质。给断奶大鼠喂食含0.1%（占总脂肪的重量/重量）神经节苷脂的半纯化日粮（处理组）或不含神经节苷脂的日粮（对照组）。喂食2周后，每个日粮组的一半动物注射生理盐水或脂多糖（LPS）内毒素（大肠杆菌血清型O111:B4，腹腔注射，3 mg/kg体重）以诱导急性肠道炎症。6小时后收集肠黏膜和血液。测定了日粮神经节苷脂对炎症黏膜和血液中促炎介质的影响，这些促炎介质包括胆固醇、血小板活化因子、前列腺素E2、白三烯B4（LTB4）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）。与注射生理盐水相比，给动物喂食对照日粮后，LPS注射后肠道脂质微区中的胆固醇含量增加了92%。与喂食对照日粮的动物相比，喂食神经节苷脂日粮的动物脂质微区中的胆固醇含量显著降低了60%。与喂食对照日粮的动物相比，通过急性全身暴露于LPS，给动物喂食神经节苷脂日粮可使炎症黏膜中的总神经节苷脂含量增加90%，同时血小板活化因子含量降低45%。当给动物喂食神经节苷脂日粮时，炎症黏膜中前列腺素E2、LTB4、IL-1β和TNF-α的水平较低，与对照动物相比，血浆中LTB4、IL-1β和TNF-α分别降低了41%、58%和55%。本研究表明，日粮神经节苷脂可抑制LPS急性炎症诱导的肠道和血液中的促炎信号，并提示其在急性局部和全身炎症性疾病的治疗和管理中的治疗潜力。
