虎杖苷对葡聚糖硫酸钠诱导小鼠溃疡性结肠炎的作用及其对Hedgehog通路影响

Effects of Polydatin on Hedgehog signaling pathway in dextran sodium sulfateinduced colitis in mice

目的探讨虎杖苷对葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导的溃疡性结肠炎(ulcerative colitis,UC)的作用及其对结肠组织中Hedgehog信号通路的影响。方法实验设置空白组、模型组、药物干预组(虎杖苷15 mg/kg、30 mg/kg、45 mg/kg) 5组,每组6只;小鼠自由饮用质量浓度为30 g/L的DSS共7 d组建UC模型,空白组正常饮水的同时予质量浓度为9 g/L的生理盐水,腹腔注射7 d;模型组造模同时予质量浓度为9 g/L的生理盐水,腹腔注射7 d;药物干预组造模同时分别予虎杖苷15 mg/kg、30 mg/kg、45 mg/kg,腹腔注射7 d。观察小鼠结肠炎相关的疾病活动指数(disease activity index,DAI)和结肠组织病理评分,RT-PCR检测小鼠结肠组织中的炎症因子IL-6、IL-17、TNF-α、IL-1β、IL-23,同时检测小鼠结肠组织中Hedgehog信号通路的转录因子Gli1 mRNA和蛋白质的表达水平。结果与模型组相比,空白组和药物干预组中DAI降低(P <0. 05);虎杖苷药物干预后结肠病理损伤明显改善;与模型组相比,药物干预组(中、高剂量)中的炎症因子IL-6、IL-17、TNF-α、IL-1β、IL-23 mRNA水平明显降低(P <0. 05),同时药物干预组中Gli1的蛋白水平明显升高,差异均有统计学意义(P <0. 05)。结论虎杖苷对DSS诱导的小鼠急性结肠炎模型具有明显的抗炎作用,其抗炎机制可能与上调Hedgehog信号通路有关。

Objective To investigate the effect of Polydatin on dextran sodium sulfate（ DSS）-induced colitis and its effect on Hedgehog signaling pathway. Methods Five groups of control group [water ＋ saline（ the mass concentration was 9 g/L）,intraperitoneally],model group [DSS ＋ saline（ the mass concentration was 9 g/L）,intraperitoneally]and drug intervention groups（ Polydatin 15 mg/kg,30 mg/kg and 45 mg/kg,intraperitoneally） were set up,6 mice in each group. The mice were taken DSS（ the mass concentration was 30 g/L） in drinking water for 7 days to establish acute colitis model. The colitis related disease activity index（ DAI） and colon histopathological score were observed. The inflammatory factors IL-6,IL-17,TNF-α,IL-1β and IL-23 in the colon were detected by RT-PCR. The transcription factor of Hedgehog signaling pathway Gli1 was detected by PT-PCR and Western blotting. Results Compared with the model group,the DAIs of the control group and the drug-intervention groups were decreased（ P〈0. 05）. The pathological damage of colon was significantly improved after the intervention of Polydatin. Compared with the model group,the expressions of IL-6,IL-17,TNF-α,IL-1β and IL-23 mRNA in the middle dose group and high dose group were significantly decreased（ P〈0. 05）. Meanwhile,the levels of Gli1 mRNA and protein were significantly increased in the drug intervention groups（ P〈0. 05）. Conclusion Polydatin exhibites obvious anti-inflammatory effect on DSS-induced acute colitis model in mice and its protective effect may be related to increase the Hedgehog signaling pathway.