盐酸青藤碱介导Hedgehog信号通路治疗小鼠溃疡性结肠炎分子机制的研究

  目的  研究盐酸青藤碱(SH)对小鼠溃疡性结肠炎(UC)的保护作用及可能机制。   方法  将24只小鼠采用随机数字表法分为正常组、模型组、SH低、高剂量组(SH 20 mg/kg、60 mg/kg)4组，每组6只；记录疾病活动指数(DAI)和结肠组织病理学评分，检测Shh mRNA及相关蛋白和细胞因子的表达。   结果  与正常组相比，模型组DAI评分(3.44±0.27)分vs. 0分, P＜0.001]升高，组织病理学评分升高(7.67±0.52)分vs. 0分，P＜0.001]，Shh mRNA降低(P＜0.05)，Shh、Smo、Ptch1、Gli1蛋白表达水平降低(均P＜0.01)，TNF-α、IL-1β、IL-6升高(均P＜0.001)；与模型组相比, SH低、高剂量组DAI评分(2.50±0.18)分、(1.89±0.17)分vs. (3.44±0.27)分, P < 0.001]降低, 组织病理学评分降低(5.17±0.75)分、(3.33±0.52)分vs. (7.67±0.52)分, P < 0.001]，Shh、Smo、Ptch1、Gli1蛋白升高(均P＜0.001)，TNF-α、IL-1β、IL-6降低(均P＜0.01)。   结论  SH可治疗小鼠UC，其机制可能是SH上调了Hedgehog信号通路活性，从而降低了TNF-α、IL-1β、IL-6含量。 

The molecular mechanism of sinomenine hydrochloride treat ulcerative colitis through Hedgehog signalling pathway in mice

  Objective  To investigate the protective effect and possible mechanism of sinomenine hydrochloride (SH) on ulcerative colitis (UC) in mice.   Methods  Twenty-four mice were randomly divided into 4 groups: normal group, model group, low and high dose SH group (SH 20 mg/kg, 60 mg/kg), with 6 mice in each group. Disease activity index (DAI) and colon histopathology (HI) scores were recorded, and the expression levels of Shh mRNA and related proteins and cytokines were detected.   Results  Compared with the normal group, the DAI score (3.44±0.27) points vs. 0, P < 0.001] and HI score (7.67±0.52) points vs. 0, P < 0.001] increased, Shh mRNA (P < 0.05), Shh, Smo, Ptch1 and Gli1 protein (all P < 0.01) decreased, and TNF-α, IL-1β and IL-6 (all P < 0.001) increased in the model group. Compared with the model group, the DAI score (2.50±0.18) points, (1.89±0.17) points vs. (3.44±0.27) points, P < 0.001], HI score (5.17±0.75) points, (3.33±0.52) points vs. (7.67±0.52) points, P < 0.001] decreased, Shh, Smo, Ptch1 and Gli1 protein (all P < 0.001) increased, and TNF-α, IL-1β, IL-6 (all P < 0.01) decreased in the SH treatment group.   Conclusion  SH can treat ulcerative colitis in mice. The mechanism may be that it up regulates the activity of Hedgehog signalling pathway, thereby reduces the content of TNF-α, IL-1β, IL-6.