神经节苷脂GD3合酶缺失加重DSS诱导的小鼠炎症性肠病

Ganglioside GD3 Synthase deficiency aggravated dextran sodium sulfate( DSS)-induced colitis

目的:探讨神经节苷脂GD3合酶(GD3S)在DSS诱导的小鼠炎症性肠病(IBD)中的作用。方法:采用7周龄C57BL/6和神经节苷脂GD3合酶缺陷(GD3S^(-/-))雄性小鼠建立葡聚糖硫酸钠(DSS)诱导的小鼠IBD模型,建模16 d检测GD3S缺失对IBD小鼠生存率的影响,建模7 d检测GD3S缺失对IBD严重程度的影响,期间每天记录小鼠体重变化以及便血情况。7 d后处死小鼠,解剖分离小鼠全结肠,测量结肠长度,苏木精-伊红(HE)染色检测小鼠结肠病理损伤,TUNEL染色检测结肠组织细胞凋亡,ELISA检测血清以及结肠组织中炎性细胞因子表达情况。结果:GD3S^(-/-)DSS模型组与WT DSS组相比,其生存率显著降低,体重下降明显加快,血便早于WT DSS组;结肠长度也显著短于WT DSS组; HE染色显示GD3S^(-/-)DSS模型组结肠黏膜组织损伤较重,TUNEL染色显示GD3S^(-/-)DSS模型组凋亡细胞显著增加; GD3S^(-/-)DSS模型组血清以及结肠黏膜组织匀浆IL-6表达明显高于WT DSS。结论:GD3S缺失会加重DSS诱导的小鼠炎症性肠病。

Objective:To investigate the effect of Ganglioside GD3 Synthase in dextran sodium sulfate(DSS)-induced colitis.Methods:DSS-induced colitis was induced with 7weeks old C57BL/6 and GD3S-/-male mice.The survival rate of Ganglioside GD3 Synthase deficiency mice was monitored over 16 days of DSS colitis induction.And the severity of DSS-induced colitis was measured in C57BL/6 and GD3S-/-mice over 7 days of DSS colitis induction.Daily changes in body weight and rectal bleeding were assessed.After 7 days of DSS colitis induction,the total colon was isolated,and then measured its length.Intestinal tissues were examined by HE and TUNEL staining to assay its pathological damage and cell apoptosis respectively.Inflammatory cytokine production of C57BL/6 and GD3S-/-mice in blood serum and colonic homogenate was detected by ELISA.Results:Compared with DSS-induced WT group,the survival rate and body weight of DSS-induced GD3S-/-group reduced significantly.The DSS-induced GD3S-/-group fecal blood also earlier than DSS-induced WT group.In the DSS-induced GD3S-/-group,the colon length obviously shortened,colonic mucosa pathological damage and cell apoptosis were more serious.Conclusion:Ganglioside GD3 Synthase deficiency aggravated the DSS-induced colitis.