药学学报, 2016, 51(10): 1558-1563
引用本文:
王敦方, 王彦礼, 王怡薇, 郭姗姗, 庄帅星, 徐航宇, 李涛, 杨伟鹏. 黄芩汤对溃疡性结肠炎大鼠TLR4/MyD88通路调控作用研究[J]. 药学学报, 2016, 51(10): 1558-1563.
WANG Dun-fang, WANG Yan-li, WANG Yi-wei, GUO Shan-shan, ZHUANG Shuai-xing, XU Hang-yu, LI Tao, YANG Wei-peng. Effect of Huangqin Tang on the function of regulatory TLR4/MyD88 signal pathway in rats with ulcerative colitis[J]. Acta Pharmaceutica Sinica, 2016, 51(10): 1558-1563.

黄芩汤对溃疡性结肠炎大鼠TLR4/MyD88通路调控作用研究
王敦方1, 王彦礼1, 王怡薇1,2, 郭姗姗1, 庄帅星1, 徐航宇1, 李涛3, 杨伟鹏1
1. 中国中医科学院中药研究所, 北京 100700;
2. 国家食品药品监督管理总局高级研修学院, 北京 100073;
3. 中国中医科学院医学实验中心, 北京 100700
摘要:
研究黄芩汤对溃疡性结肠炎(UC)大鼠TLR4/Myd88通路及下游细胞因子表达的影响,探讨其治疗效果及作用机制。运用复合法(三硝基苯磺酸+乙醇)制备细胞免疫反应UC大鼠模型;将大鼠随机分为正常对照组、模型组、阳性药柳氮磺胺吡啶组(SASP)和黄芩汤(HQT)高中低剂量组(20、10、5 g·kg-1)。治疗3天后,采用Griess法测定血清中NO含量,ELISA法测定血清中炎症介质IL-4、IL-10、IL-17和PGE2含量;治疗5天后,处死大鼠取结肠,运用免疫组化法检测COX-2、iNOS蛋白的阳性表达,采用Western blot法检测大鼠结肠TLR4、MyD88的蛋白表达。结果显示,模型组血清中NO、IL-17、PGE2水平,结肠组织TLR4、MyD88蛋白表达量及COX-2、iNOS阳性表达均高于正常组(P<0.05);黄芩汤高剂量组大鼠上述指标均较模型组显著好转(P<0.05)。说明黄芩汤对溃疡性结肠炎的治疗作用可能是通过抑制TLR4/Myd88/NF-κB通路活化,进而下调促炎细胞因子NO、IL-17和PGE2表达实现的。
关键词:    黄芩汤      溃疡性结肠炎      TLR4      MyD88      细胞因子     
Effect of Huangqin Tang on the function of regulatory TLR4/MyD88 signal pathway in rats with ulcerative colitis
WANG Dun-fang1, WANG Yan-li1, WANG Yi-wei1,2, GUO Shan-shan1, ZHUANG Shuai-xing1, XU Hang-yu1, LI Tao3, YANG Wei-peng1
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China;
2. China Food and Drug Administration Institute of Executive Development, Beijing 100073, China;
3. The Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China
Abstract:
This study was designed to investigate the effect of Huangqin Tang (HQT) on TLR4/Myd88 pathway and the downstream cytokines in rats with ulcerative colitis (UC) to explore its underlying mechanisms of action. The model of UC rats with cell immunoreactivity was made using a compound method (trinitrobenzene sulfonic acid plus ethanol). Rats were randomly divided into the control group, the model group, the salazosulfapyridine (SASP) group, high, medium and low dose (20, 10, 5 g·kg-1) of HQT groups. After a three-day treatment, production of NO in serum was detected by Griess assay, the levels of interleukin (IL)-4, IL-10, IL-17 and prostaglandin E2 (PGE2) in serum were detected by ELISA. After a five-day treatment, the positive protein expressions of COX-2 and iNOS in the colon tissue were determined by ICH method, the protein expressions of TLR4 and MyD88 in colon tissue were determined by Western blot. Compared with the control group, the levels of NO, IL-17, PGE2, the protein expressions of TLR4, MyD88 and the protein positive expressions of COX-2, iNOS were apparently higher in the model group. Compared with model group, the above indexes were significantly improved in the SASP and high-dose HQT groups (P<0.05). These results show that HQT has a definite effect on UC in rats. Its mechanisms of action may be achieved by inhibiting the activity of TLR4/MyD88/NF-κB signal pathway and down-regulation of NO, IL-17 and PGE 2 production.
Key words:    Huangqin Tang    ulcerative colitis    TLR4    MyD88    cytokine   
收稿日期: 2016-05-17
DOI: 10.16438/j.0513-4870.2016-0480
基金项目: 国家自然科学基金资助项目(81273662,81473592).
通讯作者: 杨伟鹏
Email: hrbywp@sina.com
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