槐果碱治疗小鼠实验性结肠炎的机制研究

对照组差异有统计学意义（P<0.05），槐果碱干预组上述指标则均较模型组明显改善（P< 0.05）。模型组TNF-α，IL-1β，IL-6较正常组明显上升（P<0.05），槐果碱干预后不同程度下调（P<0.05）。正常组中TLR4蛋白表达量少，P38，JNK1/2，JAK2，STAT3蛋白磷酸化水平低下，模型组中TLR4蛋白表达上调，P38，JNK1/2，JAK2，STAT3蛋白磷酸化水平升高，槐果碱干预组TLR4表达较模型组减少，P38，JNK1/2，JAK2，STAT3磷酸化水平较模型组明显下调。结果表明，槐果碱能抑制TLR4/MAPKs，JAK2/STAT3信号通路活化，减少肠道组织中促炎细胞因子TNF-α，IL-1β，IL-6表达，减轻炎性反应，从而有效防治实验性结肠炎。

[关键词] 溃疡性结肠炎;槐果碱;Toll样受体4;促分裂原活化蛋白激酶;蛋白酪氨酸激酶2;信号转导和转录激活因子3

[收稿日期] 2014-11-05

[通信作者] *陈岳祥，E-mail：chenyuexiang@hotmail.com

[作者简介] 张剑美，E-mail：zjmyeah@163.com

Mechanism of sophocarpine in treating experimental colitis in mice

ZHANG Jian-mei1， ZHU Ya-bi1， DENG Xing2， WANG Chang-xiong1， LUAN Shuang-mei1， CHEN Yue-xiang2*

（1. Department of Gastroenterology， Lishui People′s Hospital， Lishui 323000， China;

2. Department of Gastroenterology， Shanghai Changzheng Hospital， Shanghai 200003， China）

[Abstract] To study the preventive effect of sophocarpine （Soc） on dextran sulfate sodium （DSS）-induced colitis in mice， in order to analyze the influence of Soc on toll like receptor 4 （TLR4）/mitogen-activated protein kinases （MAPKs） and janus tyrosine kinase 2 signal transducer and activator of transcription 3 （JAK2/STAT3） signal pathways in mice intestinal tissues. The mice was given 2.5% DSS for 6 days to induce the acute colitis model. The Soc-treated group was intraperitoneally injected with sophocarpine 30 mg·kg^-1·d^-1 since the day before the experiment to the end. The disease activity index （DAI） was assessed everyday， and the colonic morphology and histological damage were observed with HE staining. The mRNA expressions of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and interleukin-6 （IL-6） were detected by real-time RT-PCR. The changes in key protein kinase p38 mitogen-activated protein kinase （p38MAPK）， c-Jun NH2-terminal protein kinase1/2 （JNK1/2）， extracellular signal-regulated kinase1/2 （ERK1/2）， JAK2， STAT3 in TLR4/MAPKs and JAK2/STAT3 signaling pathways were detected by western blot. The result showed that the model group showed statistical significance in body weight， DAI， colon length and histopathological changes compared with the normal group （P<0.05）; however， the Soc-treated group showed significant improvements in the above indexes compared with the model group （P<0.05）. TNF-α， IL-1β and IL-6 in the model group was significantly higher than that in the normal group （P<0.05）， but lowered in the Soc-treated group to varying degrees （P<0.05）. In the normal group， the expressions of TLR4 and the phosphorylation of P38， JNK1/2， JAK2， STAT3 were at low levels; in the model group， the phosphorylation of P38， JNK1/2， JAK2， STAT3 increased; the Soc-treated group showed a decrease in TLR4 expression compared with the model group， with notable declines in the phosphorylation of TLR4， P38， JNK1/2， JAK2， STAT3. These findings indicate that Soc can inhibit TLR4/MAPKs， K2/STAT3 signaling pathway activation， reduce the expression of proinflammatory cytokines TNF-α， IL-1β and IL-6 and relieve inflammatory reactions， so as to effectively prevent experimental colitis.

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