药学学报, 2015, 50(1): 21-27
引用本文:
王怡薇, 张会会, 王彦礼, 郭姗姗, 李涛, 陈立, 庄帅星, 周钟鸣, 杨伟鹏. 黄芩汤对溃疡性结肠炎大鼠NF-κBp65调控作用研究[J]. 药学学报, 2015, 50(1): 21-27.
WANG Yi-wei, ZHANG Hui-hui, WANG Yan-li, GUO Shan-shan, LI Tao, CHEN Li, ZHUANG Shuai-xing, ZHOU Zhong-ming, YANG Wei-peng. Effect of Huangqin Tang on the regulatory NF-κB p65 signal pathway in rats with ulcerative colitis[J]. Acta Pharmaceutica Sinica, 2015, 50(1): 21-27.

黄芩汤对溃疡性结肠炎大鼠NF-κBp65调控作用研究
王怡薇1, 张会会1, 王彦礼1, 郭姗姗1, 李涛2, 陈立1, 庄帅星1, 周钟鸣1, 杨伟鹏1
1. 中国中医科学院 中药研究所, 北京 100700;
2. 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) 大鼠细胞因子、NF-κB p65蛋白表达的影响, 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) 制备细胞免疫反应性UC大鼠模型, 大鼠随机分成正常对照组、模型组、柳氮磺胺吡啶 (SASP) 组和黄芩汤高、中、低剂量组 (20、10、5 g·kg-1)。治疗5天后评估各组大鼠饮食量、体重变化及组织损伤程度, 采用Griess法测定血清中NO含量, ELISA法测定IL-6、TNF-α、PGE2含量, 运用免疫组化法检测NF-κB p65蛋白表达情况。结果显示, 模型组大鼠饮食量及体重显著低于正常组; 血清中NO、IL-6、TNF-α、PGE2水平、结肠组织NF-κB p65蛋白表达量及组织损伤程度显著高于正常组。黄芩汤高、中剂量组大鼠上述指标均较模型组显著好转。黄芩汤对溃疡性结肠炎的治疗作用可能是通过抑制NF-κB P65通路活化, 进而下调促炎细胞因子NO、IL-6、TNF-α和PGE2表达实现的。
关键词:    黄芩汤      溃疡性结肠炎      NF-κB p65      细胞因子     
Effect of Huangqin Tang on the regulatory NF-κB p65 signal pathway in rats with ulcerative colitis
WANG Yi-wei1, ZHANG Hui-hui1, WANG Yan-li1, GUO Shan-shan1, LI Tao2, CHEN Li1, ZHUANG Shuai-xing1, ZHOU Zhong-ming1, YANG Wei-peng1
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China;
2. The Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China
Abstract:
To investigate the effect of Huangqin Tang on expression of cytokines and NF-κB p65 in rats with ulcerative colitis (UC), and to probe into its underlying mechanisms of action. The mode of UC rats with cell immunoreactivity was made using compound method (trinitrobenzene sulfonic acid and ethanol). Rats were randomly divided into control group, model group, SASP group and high dose, middle dose and low dose of Huangqin Tang group. The food intake, body weight and microscopic damage of rats in each group were evaluated after being treated for five days. The blood and colon tissue were also collected. Production of NO was detected by Griess assay, the expression levels of IL-6, TNF-α, PGE2 were detected by ELISA. ICH method was undertaken to determine the expression of NF-κB p65 protein in colon tissue. The food intake and body weight of model group rats were lower than that of control group. The expression levels of NO, IL-6, TNF-α, PGE2 in serum and NF-κB p65 protein of colon tissue in model group were higher than that of control group. The above indexes were ameliorated in high and middle dose of Huangqin Tang groups. But there was no significant difference with SASP group. NF-κB p65 may be involved in the pathogenesis of UC, and Huangqin Tang can inhibit the relative activity of NF-κB p65, and decrease the expression levels of NO, IL-6, TNF-α and PGE2.
Key words:    Huangqin Tang    ulcerative colitis    NF-κB p65    cytokines   
收稿日期: 2014-05-26
基金项目: 国家自然科学基金资助项目 (81273662, 30801542); 中国中医科学院自主业务选题项目 (ZZ2007046).
通讯作者: 杨伟鹏
Email: hrbywp@sina.com
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参考文献:
[1] Chow DKL, Leong RWL, Tsoi KKF, et al. Long-term follow-up of ulcerative colitis in the Chinese population [J]. Am J Gastroenterol, 2009, 104: 647-654.
[2] Ukil A, Maity S, Das PK. Protection from experimental colitis by theaflavin-3, 3'-digallate correlates with inhibition of IKK and NF-κB activation [J]. Br J Pharmacol, 2006, 149: 121-131.
[3] Huang L, Ye WH, Cai BW, et al. A preliminary study on the pharmacology of the compound prescription Huangqin Tang and its component drugs [J]. China J Chin Mater Med (中国中药杂志), 1990, 15: 51-53, 64.
[4] Yu XF, Lü XZ, Dong WB. Clinical observation of ulcerative colitis treated by Huangqin Tang [J]. J Emerg Tradit Chin Med (中国中医急症), 2010, 19: 1510, 1529.
[5] Sohn KH, Jo JM, Cho WJ, et al. Bojesodok-eum, a herbal prescription, ameliorates acute inflammation in association with the inhibition of NF-κB-mediated nitric oxide and proin­flammatory cytokine production [J]. Evid-Based Complement Alternat Med, 2012: 457370.
[6] Cortez M, Carmo LS, Rogero MM, et al. A high-fat diet increases IL-1, IL-6, and TNF-α production by increasing NF-κB and attenuating PPAR-γ expression in bone marrow mesenchymal stem cells [J]. Inflammation, 2013, 36: 379- 386.
[7] Jobin C, Sartor RB. NF-κB signaling proteins as therapeutic targets for inflammatory bowel diseases [J]. Inflamm Bowel Dis, 2000, 6: 206-213.
[8] Li T. Study on the Chemical Basis and Pharmacokinetics of Huangqin Tang (黄芩汤物质基础与药代动力学特征研究) [D]. Beijing: China Academy of Chinese Medical Sciences, 2013.
[9] Morris GP, Beck PL, Herridge MS, et al. Hapten-induced model of chronic inflammation and ulceration in the rat colon [J]. Gastroenterology, 1989, 96: 795-803.
[10] Chen ZN, Shen MC, Guo MY. Practical Surgical Pathology (实用外科病理学) [M]. Shanghai: Shanghai Medical University Publishing House, 1997: 676-681.
[11] Yu BJ, Wang ZQ. The Preclinical Safety Evaluation and Practice (新药临床前安全性评价与实践) [M]. Beijing: Military Medical Sciences Publishing House, 1997: 78-80.
[12] Zhang BG, Li XX, Liu QF. Modern pharmacodynamics research and clinic application of Huangqin Tang [J]. China J Chin Mater Med (中国中药杂志), 2008, 33: 2587-2590.
[13] Zhou YP, Yang ZJ, Chen C, et al. Clinical observation of effect of Huangqin Tang plus on regulating T cells subpopulations of ulcerative colitis patients [J]. Gansu J Tradit Chin Med (甘肃中医), 2004, 17: 32-34.
[14] Lu ZY, Zhong NS. Internal Medicine (内科学) [M]. 7th Ed. Beijing: People's Medical Publishing House, 2008: 410-414.
[15] Felley-Bosco E, André M. Proteomics and chronic inflammatory bowel diseases [J]. Pathol Res Pract, 2004, 200: 129-133.
[16] Liu DQ, Wu CQ, Shi W, et al. Sufferer's chang in tumor necrosis factor, interleukin-8, nitric oxide synthase and nitric oxide of ulcerative colitis [J]. Clinic Focus, 2006, 21: 114- 115.
[17] Papadakis KA, Targan SR. Tumor necrosis factor: biology and therapeutic inhibitors [J]. Gastroenterology, 2000, 119: 1148-1157.
[18] Halter F, Tarnawski AS, Schmassmann A, et al. Cyclooxy­genase 2-implications on maintenance of gastric mucosal integrity and ulcer healing: controversial issues and perspectives [J]. Gut, 2001, 49: 443-453.
[19] Chen YC, Yang LL, Lee TJF. Oroxylin A inhibition of lipopolysaccharide-induced iNOS and COX-2 gene expression via suppression of nuclear factor-κB activation [J]. Biochem Pharm, 2000, 59: 1445-1457.
[20] Chen YC, Shen SC, Chen LG, et al. Wogonin, baicalin, and baicalein inhibition of inducible nitric oxide synthase and cyclooxygenase-2 gene expressions induced by nitric oxide synthase inhibitors and lipopolysaccharide [J]. Biochem Pharm, 2001, 61: 1417-1427.
[21] Chi YS, Cheon BS, Kim HP. Effect of wogonin, a plant flavone from Scutellaria radix, on the suppression of cyclooxygenase-2 and the induction of inducible nitric oxide synthase in lipopolysaccharide-treated RAW 264.7 cells [J]. Biochem Pharmacol, 2001, 61: 1195-1203.
[22] Kang BY, Chung SW, Kim SH, et al. Involvement of nuclear factor-κB in the inhibition of interleukin-12 production from mouse macrophages by baicalein, a flavonoid in Scutellaria baicalensis [J]. Planta Med, 2003, 69: 687-691.
[23] Lin CC, Shieh DE. The anti-inflammatory activity of Scutellaria rivularis extracts and its active components, baicalin, baicalein and wogonin [J]. Am J Chin Med, 1996, 24: 31-36.
[24] Wakabayashi I, Yasui K. Wogonin inhibits inducible prostaglandin E2 production in macrophages [J]. Eur J Pharm, 2000, 406: 477-481.
[25] Zhang DY, Wu J, Ye F, et al. Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis [J]. Cancer Res, 2003, 63: 4037-4043.