趋化因子SLC在小鼠实验性结肠炎中的表达和意义

Expression and Significance of Chemokine SLC in Mice with Experimental Colitis

背景:次级淋巴组织趋化因子(SLC)是一种CC型趋化因子,主要功能为趋化各种淋巴细胞向外周淋巴组织或器官归巢。既往研究发现结肠组织SLC表达增高可能参与了溃疡性结肠炎(UC)的发病。目的:明确SLC在UC中的作用及其作为UC治疗靶点的可能性。方法:24只雌性BALB/c小鼠随机分为对照组、DSS模型组和地塞米松(DXM)治疗组,后两组饮用5%DSS溶液7 d诱导实验性结肠炎以模拟人类UC,DXM治疗组于造模第3 d起腹腔注射DXM 0.4 mg/kg qd×5 d。实验过程中评估疾病活动指数(DAI)。第8 d处死各组小鼠,行结肠大体形态和组织学评分,以免疫组化染色和RT-PCR检测结肠组织SLC表达。结果:对照组结肠组织SLC表达微弱,DSS模型组SLC mRNA和蛋白表达均较对照组显著上调(P<0.01),DXM治疗组SLC表达较DSS模型组显著降低(P<0.01),伴DAI以及结肠大体形态和组织学评分改善(P<0.01)。结论:结肠组织SLC表达增高与UC发病有关,针对SLC的靶向治疗可作为UC的治疗选择。

Background： Secondary lymphoid-tissue chemokine （SLC） is a member of CC chemokines that mainly contributes to the homing of various lymphocytes to peripheral lymphoid tissues and organs. Previous studies demonstrated that overexpression of SLC in colonic tissue might be involved in the pathogenesis of ulcerative colitis （UC）. Aims： To clarify the role of SLC in UC and whether it can be used as a therapeutic target for UC. Methods： Twenty-four female BALB/c mice were randomly divided into three groups： control group, DSS model group and dexamethasone （DXM） treatment group. Mice in DSS model group and DXM treatment group drank 5% DSS solution for 7 days to induce experimental colitis mimicking human UC. From the 3rd day of model construction, mice in DXM treatment group were given DXM 0.4 mg/kg ip qd for 5 days. Disease activity index （DAI） was assessed during the experimental course. All the mice were sacrificed on day 8, scores of macropathology and histopathology of the colon were evaluated. Expression of SLC in colonic tissue was examined by immunohistochemistry and RT-PCR. Results： Expression of SLC was extremely faint in colonic tissue of mice in control group, and was significantly up-regulated at both mRNA and protein levels in mice in DSS model group （P〈0.01）. DXM treatment decreased the expression of SLC and improved the DAI and colonic macropathological and histopathological scores （P〈0.01）. Conclusions： Overexpression of SLC in colonic tissue is correlated with the pathogenesis of UC and SLC targeted therapy might be used for UC treatment.