摘要
目的:研究盐酸青藤碱对葡聚糖硫酸钠诱导的实验性结肠炎小鼠的治疗作用。方法:制备实验性结肠炎小鼠模型,随机分为空白对照组、葡聚糖硫酸钠(DSS)模型对照组、柳氮磺吡啶组及青藤碱低、中、高剂量组(n=6)。空白对照组与DSS模型对照组每天给予生理盐水0.2ml,柳氮磺吡啶组(100 mg·kg^(-1)),青藤碱低剂量组(30 mg·kg^(-1))、中剂量组(90 mg·kg^(-1))、高剂量组(270 mg·kg^(-1)),连续灌胃10d。评价各组小鼠疾病活动指数(DAI)和组织学损伤评分,Western-blotting检测结肠组织中Toll样受体4(TLR4)、髓样分化因子(Myd88)表达,免疫组织化学法检测结肠组织中核转录因子-κB(NF-κB)的表达。结果:DSS模型对照组小鼠DAI和组织损伤评分、结肠组织中TLR4、Myd88、NF-κB表达均显著高于空白对照组(P<0.01),柳氮磺吡啶组和青藤碱低、中、高剂量组均能降低DAI和组织损伤评分,降低结肠组织中TLR4、Myd88、NF-κB表达(P<0.01),且呈浓度依赖性。柳氮磺吡啶组与青藤碱中、高剂量组间差异无统计学意义(P>0.05)。结论:青藤碱能通过影响实验性结肠炎小鼠TLR4/NF-κB信号通路,降低TLR4、Myd88、NF-κB表达,发挥治疗作用。
Objective: To study the effect of sinomenine hydrochloride on dextran sulfate sodium (DSS) induced experimental colitis in mice. Methods: The colitis model of BALB/c mice was established with DSS. The mice were randomly divided into six groups (n = 6) : the normal control group and the model group (giving normal saline, 0.2 ml), salieylazosulfapyridine treatment group (100 mg ·kg-1 ) and sinomenine treatment groups (30, 90, 270 mg ·kg-1 ). After continuous administration for 10 d, the disease activity index (DAI) and the tissue damage index in each group were evaluated. The mouse colons of TLR4 and Myd88 were detected using Western-blotting, and the expression of NF-κB in the colon tissues was detected using immunohistochemical method. Results: The DAI and the tissue damage index, and the expressions of TLR4, Myd88 and NF-κB in the colon tissues were significantly higher in the model group than those in the normal group (P 〈 0.01). Sulfasalazine treatment group and sinomenine at low, medium and high dose groups could reduce the DAI and the tissue damage score, and the expressions of TLR4, Myd88 and NF-κB in the colon tissues (P 〈 0.01) in a concentration-dependent manner. There was no significant difference between salicylazosulfapyridine treatment group and sinomenine at medium/high dose groups. Conclusion: Sinomenine reduces the expression of TLR4, Myd88 and NF-κB in mice with experimental colitis by regulating the TLR4/NF- k B signaling pathway to play a therapeutic role.
作者
田亮
薛洁
刘丽丽
余意
傅颖珺
Tian Liang;Xue Jie;Liu Lili;Yu Yi;Fu Yingjun(Shanghai Deji Hospital, No. 9 Clinical Medical School of Qingdao University, Shanghai 200331, China;Department of Pharmaceutical Science, Nanchang University)
出处
《中国药师》
CAS
2018年第5期797-801,共5页
China Pharmacist