槐果碱治疗小鼠实验性结肠炎的机制研究  

Mechanism of sophocarpine in treating experimental colitis in mice

作　　者：张剑美[1] 朱雅碧[1] 邓星[2] 王昌雄[1] 栾双梅[1] 陈岳祥[2] 

机构地区：[1]丽水市人民医院消化内科,浙江丽水323000 [2]上海长征医院消化内科,上海200003

出　　处：《中国中药杂志》2015年第15期3081-3087,共7页China Journal of Chinese Materia Medica

摘　　要：研究槐果碱对葡聚糖硫酸钠(DSS)诱导的小鼠急性结肠炎的防治作用,探讨槐果碱对小鼠肠道组织中Toll样受体4(TLR4)/促分裂原活化蛋白激酶(MAPKs)和蛋白酪氨酸激酶2/信号转导和转录激活因子3(JAK2/STAT3)信号通路的影响。采用2.5%DSS饮用6 d诱导小鼠急性结肠炎模型,实验前1天及实验全程中槐果碱组给予腹腔内注射槐果碱30 mg·kg-1·d-1,每日进行疾病活动指数(DAI)评分,HE染色观察小鼠结肠黏膜大体形态和组织病理学损伤情况;Real-time RT-PCR法检测各组小鼠肠黏膜肿瘤坏死因子-α(TNF-α),白介素-1β(IL-1β)及白介素-6(IL-6)mRNA表达情况;Western blot检测各组小鼠肠黏膜组织中TLR4/MAPKs及JAK2/STAT3信号通路中重要蛋白激酶P38丝裂原活化蛋白激酶(p38MAPK),c-Jun氨基端激酶1/2(JNK1/2),细胞外信号调节激酶1/2(ERK1/2),JAK2及STAT3变化情况。结果显示,模型组小鼠体重,DAI,结肠长度及组织病理学变化较正常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。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 2signal 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-1since 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 thephosphorylation 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 indica

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 

分 类 号：R285.5[医药卫生—中药学]