GSH在DSS诱导的小鼠实验性肠炎中的作用

Roles of Glutathione in dextran sodium sulphate-induced colitis in mice

目的:探讨硫酸葡聚糖钠(dextransodiumsulphate,DSS)诱导的小鼠肠炎模型病变结肠组织的谷胱甘肽(GSH)变化及其与病变组织分泌的Th1/Th2型细胞因子IFN-γ,IL-4及黏膜损伤的关系.方法:实验组小鼠(n=10)给予含50g/LDSS的蒸馏水自由饮用7d之后处死,分离出的病变结肠一部分评价其病理学改变并用GSH1抗体做免疫组化,另一部分结肠培养后检测其IL-4、IFN-γ的表达.对照组小鼠(n=10)给予蒸馏水自由饮用7d之后处死.结果:DSS诱导实验性肠炎小鼠口服50g/L的DSS溶液7d出现体重减轻、腹泻、血便等急性肠炎的表现.病理学切片HE染色发现小鼠病变结肠腺体结构紊乱,黏膜和黏膜下单核细胞和多核细胞浸润.DSS组病变肠段组织GSH表达较对照组明显减少(2±0.6vs3.14±1.0,t=3.95,P=0.01<0.05),病变结肠分泌的IL-4明显升高(38.7±4.7vs28.7±6.7,t=3.16,P=0.009<0.01),IFN-γ轻度降低(P>0.05).结论:DSS诱导的实验性肠炎小鼠病变结肠组织GSH的减少与病变结肠组织分泌的细胞因子IL-4增加、IFN—γ下降以及黏膜损伤相关.

AIM: To investigate the expression of glutathione (GSH) in dextran sodium sulphate(DSS)-induced colitic mucosa and its relationship with cytokine secretion as well as mucosal injury. METHODS: BALB/c mice in DSS group (n = 10) were fed with 50 g/L DSS to induce experimental colitis and those in normal controls (n = 10) were fed with distilled water. All the mice were killed after 7 days. The pathological changes of the colonic tissues were examined while immunohi-stochemstry was performed with GSH1 antibody to determine the GSH expression. ELISA was used to detect the expression of IL-4 and IFN-γ. RESULTS: The manifestations of acute colitis such as weight decrease, diarrhea and bloody stool appeared in mice of DSS group, focal crypt lesionsPathologically, focal crypt distortion, granulocyte and macrophage invasion were observed. The level of GSH in DSS group was significantly lower than that in control group (2±0.6 vs 3.14±1.0, t = 3.95, P = 0.01), whereas the expres- sion of IL-4 was marked higher (38.7±4.7 vs28.7±6.7, t= 3.16, P = 0.009). The content of IFN-γwas decreased in DSS group (P>0.05). CONCLUSION: Low expression of GSH is related to the increase of IL-4, decrease of IFN-γand mucosal injury in DSS-induced colitis in mice.