炎症性肠病患者神经节苷脂分解代谢增加及不饱和度降低。
Increased catabolism and decreased unsaturation of ganglioside in patients with inflammatory bowel disease.
作者信息
Miklavcic John J, Hart Tasha D L, Lees Gordon M, Shoemaker Glen K, Schnabl Kareena L, Larsen Bodil M K, Bathe Oliver F, Thomson Alan B R, Mazurak Vera C, Clandinin M Tom
机构信息
John J Miklavcic, Glen K Shoemaker, Vera C Mazurak, M Tom Clandinin, Alberta Institute for Human Nutrition, University of Alberta, Edmonton AB T6G 2R1, Canada.
出版信息
World J Gastroenterol. 2015 Sep 21;21(35):10080-90. doi: 10.3748/wjg.v21.i35.10080.
AIM
To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease.
METHODS
Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease (n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps (n = 6) and colorectal cancer (n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine (PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A (HEXA) and sialidase-3 (NEU3) were measured in intestinal mucosa using western blot and compared among subject groups.
RESULTS
Relative GM3 ganglioside content was 2-fold higher (P < 0.05) in intestine from patients with inflammatory bowel disease (IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue (P < 0.05). Control intestine exhibited 3-fold higher (P < 0.01) relative GD1a ganglioside content than IBD intestine. GD3 and GD1a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine (P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold (P < 0.05) and NEU3 was increased 8.3-fold (P < 0.01) compared to normal intestine. Intestinal mucosa in IBD is characterized by increased GM3 content, decreased GD1a, and a reduction in polyunsaturated fatty acid constituents in GD3, GD1a and PC.
CONCLUSION
This study suggests a new paradigm by proposing that IBD occurs as a consequence of increased metabolism of specific gangliosides.
目的
研究神经节苷脂的加速分解代谢和神经节苷脂含量降低是否促成促炎性肠道疾病的病因。
方法
在这项观察性病例对照研究中，从接受肠切除术的溃疡性结肠炎或炎性克罗恩病患者（n = 11）获取回肠末端或结肠的肠黏膜，并与来自良性结肠息肉患者（n = 6）和结直肠癌患者（n = 12）的正常肠对照样本进行比较。使用液相色谱三重四极杆质谱法，根据类别以及神经酰胺或脂肪酸组成对肠黏膜的神经节苷脂和磷脂进行表征。比较各受试者组中神经节苷脂类别GM1、GM3、GD3、GD1a、GT1和GT3的含量及组成。比较各受试者组中磷脂类别磷脂酰胆碱（PC）和磷脂酰乙醇胺的含量及组成。计算并比较各受试者组中单个神经节苷脂和磷脂类别的不饱和度指数。使用蛋白质免疫印迹法检测肠黏膜中的神经节苷脂分解代谢酶β-己糖胺酶A（HEXA）和唾液酸酶-3（NEU3），并比较各受试者组。
结果
与对照肠相比，炎性肠病（IBD）患者的肠中GM3神经节苷脂相对含量高出2倍（P < 0.05）。IBD肠中GM3的量及GM3/GD3的比值也高于对照组织（P < 0.05）。对照肠中GD1a神经节苷脂相对含量比IBD肠高出3倍（P < 0.01）。对照肠中存在含有三个不饱和键的神经节苷脂GD3和GD1a种类，但在IBD肠中未检测到。IBD肠中含有两个以上不饱和键的PC相对含量比对照肠低30%（P < 0.05）。与正常肠相比，IBD肠中HEXA的相对含量增加了1.7倍（P < 0.05），NEU3增加了8.3倍（P < 0.01）。IBD中的肠黏膜特征为GM3含量增加、GD1a减少以及GD3、GD1a和PC中的多不饱和脂肪酸成分减少。
结论
本研究提出了一种新的模式，即IBD是特定神经节苷脂代谢增加的结果。
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