盐酸小檗碱对葡聚糖硫酸钠所致小鼠结肠炎的作用研究

盐酸小檗碱对葡聚糖硫酸钠所致小鼠结肠炎的作用研究

舒德忠, 万先惠, 刘华蓉, 杨俊卿, 周岐新^*

1.重庆涪陵中心医院, 重庆涪陵 408000;
2.重庆市巴南区第二人民医院, 重庆 430054;
3.重庆医科大学药理教研室, 重庆 400016

收稿日期:2006-03-12 修回日期:2006-08-10 出版日期:2006-09-15 发布日期:2006-09-15
通讯作者: 周岐新*

Effect of Berberine Chloride on Experimental Murine Colitis Induced by Dextran Sulfate Sodium

SHU De-zhong, WAN Xian-hui, LIU Hua-rong, YANG Jun-qing, ZHOU Qi-xin^*

1.The Central Hospital of Fuling County, Chongqing 408000, China;
2.The Second People′s Hospital of Banan County, Chongqing 430054, China;
3.Department of Pharmacology, Chongqing University of Medical Sciences, Chongqing 400016, China

Received:2006-03-12 Revised:2006-08-10 Online:2006-09-15 Published:2006-09-15
Contact: ZHOU Qi-xin*

摘要/Abstract

摘要： 目的研究盐酸小檗碱对小鼠实验性溃疡性结肠炎的保护作用。方法实验设正常、模型、柳氮磺胺吡啶(SASP, 520 mg·kg^-1)和盐酸小檗碱(berberine chloride, BER)低、中、高(15 mg·kg^-1、45 mg·kg^-1、150 mg·kg^-1)剂量组。六组小鼠自由饮用4%葡聚糖硫酸钠(dextran sulphate sodium, DSS)水溶液或蒸馏水, 同时分别灌胃给予干预药物或溶剂(0.2 mL/10 gWt, 1次/d×7 d)。以疾病活动指数(Disease activity index, DAI)评价小鼠临床症状。生化方法测定结肠组织MDA含量, SOD、MPO活性; HE染色切片, 评估结肠组织病理改变; 免疫组化检测ICAM-1、NF-κB p65蛋白表达水平。结果模型组DAI显著增高, 结肠黏膜损伤严重; MDA含量、MPO活性及ICAM-1和NF-κB p65表达明显升高, SOD活性下降。SASP 520 mg·kg-1能明显逆转上述情况改变; BER使DAI减小, 结肠黏膜损伤减轻, MDA含量、MPO活性降低, 阻遏ICAM-1和NF-κB p65蛋白表达, 升高SOD活性, 且呈现一定剂量依赖性。结论 BER可能通过抗氧自由基作用, 抑制ICAM-1表达及NF-κB激活, 缓解DSS所致的小鼠结肠炎症。,

关键词: 葡聚糖硫酸钠, 葡聚糖硫酸钠, 葡聚糖硫酸钠, 盐酸小檗碱, 盐酸小檗碱, 盐酸小檗碱, 溃疡性结肠炎, 溃疡性结肠炎, 溃疡性结肠炎, BALB/C小鼠, BALB/C小鼠, BALB/C小鼠

Abstract: Aim To investigate the effect in berberine chloride (BER) on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium (DSS) solution or distilled water freely with different doses of BER (15 mg·kg^-1, 45 mg·kg^-1, 150 mg·kg^-1) or salicylazosulfapyridine (SASP, 520 mg·kg^-1), and solvent (0.2 mL/10 mg Wt) once a day for 7 d, respectively. The symptom of ulcerative colitis was evaluated by disease activity index (DAI). Myeloperoxidase (MPO) and superoxide dismutase (SOD) activities and malondialdehyde (MDA) content were determined by HE staining and immunohistochemistry of expressions of NF-κB p65 and intercellular adhesion molecule 1(ICAM-1) proteins to observe the damage to colon tissues and possible mechanisms. Results DAI, MPO activity, MDA content and expressions of ICAM-1 and NF-κB p65 were markedly increased, while SOD activity decreased in DSS-treated mice. Treatment of mice with different doses of BER or SASP significantly decreased DAI, MPO activity and MDA content, improved histological changes of colon tissues, blunted the expressions of NF-κB p65 and ICAM-1 proteins, and enhanced SOD activity. Conclusion Berberine chloride has excellent therapeutic effect on ulcerative colitis caused by DSS in mice. The possible mechanism may be related to its antioxidant and anti-inflammatory activities associated with inhibiting the NF-κB activation and ICAM-1 expression.

Key words: berberine chloride, berberine chloride, ulcerative colitis, ulcerative colitis, dextran sulfate sodium, dextran sulfate sodium, BALB/C mice, BALB/C mice

中图分类号:

R965

Supporting: Foundation item: A Project of the Health Bureau of Chongqing (No.2004-B-31)
^*Corresponding author. Tel.: 86-23-68485038

舒德忠, 万先惠, 刘华蓉, 杨俊卿, 周岐新^*. 盐酸小檗碱对葡聚糖硫酸钠所致小鼠结肠炎的作用研究[J]. .

SHU De-zhong, WAN Xian-hui, LIU Hua-rong, YANG Jun-qing, ZHOU Qi-xin^*. Effect of Berberine Chloride on Experimental Murine Colitis Induced by Dextran Sulfate Sodium[J]. .

参考文献

[1] Mckenzie SJ, Baker MS, Buftton GD, et al. Evidence of oxidant-induced injury to epithelial cells during inflammatory bowel disease [J]. J Clin Invest, 1996, 98: 136-141.
[2] Sutherland LR, May GR, Shafter EA. Sulfasalazine revisited: a meta-analysis of 5-aminosalicylic acid in the treatmen of ulcerative colitis [J]. Ann Intern Med, 1993, 118: 540-549.
[3] Wang LM, Yamamoto T, Wang XX, et al. Effects of Oren-gedoku-to and Unsei-in, Chinese traditional medicines, on interleukin-8 and superoxide dismutase in rat [J]. J Pharm Pharmacol, 1997, 49: 102-104.
[4] Zhou H, Mineshita S. The effect of berberine chloride on experimental colitis in rats in vivo and in vitro [J]. J Pharmacol Exp Ther, 2000, 294 (3) : 822-829.
[5] Zhou H, Mineshita S. The effect of Oren-gedoku-to on experimental colitis in rats [J]. J Pharm Pharmacol, 1999, 51 (9) : 1065-1074.
[6] Cooper HS, Murthy SN, Shah RS, et al. Clinicopathologic study of dextran sulfate sodium experimentalmurine colitis [J]. Lab Invest, 1993, 69: 238-249.
[7] Mckenzie SJ, BakerMS, Buftton GD, et al. Evidence of oxidant-induced injury to ep ithelial cells during inflammatory bowel disease [J]. J Clin Invest, 1996, 98: 136-141.
[8] Keshavarzian A, Morgan G, Sedghi S, et al. Role of reactive oxygen metabolites in experimemtal colitis [J]. Gut, 1990, 31: 786-790.
[9] Grisham MB. Oxidants and free radicals in inflammatory bowel disease [J]. Lancet, 1994, 344: 859-861.
[10] Krawisz JE, Sharon P, Stenson WF. Quantitative assay for actute intestinal inflammation based on myeloperoxidase activity [J]. Gastroenterology, 1984, 87: 1344-1350.
[11] Bendjelloul F, Maly P, Mandys M, et al. Intercellular adhesion molecule-1 ( ICMA-1 ) deficiency protects mice against severe forms of experimentally induced colitis [J]. Clin Exp Immunol, 2000, 119: 57-63.
[12] Taniguchi T, Tsukada H, Nakamura H, et al. Effects of the anti-ICAM-1 monoclonal antibody on dextran sodium sulphate-induced colitis in rats [J]. J Gastroenterol Hepatol, 1998, 13 (9) : 945-949.
[13] Jobin C, Sartor RB. The IkappaB/NF-kappaB system: a key determinant of mucosal inflammation and protection [J]. Am J Physiol Cell Physiol, 2000, 278: C451-462.
[14] Segain JP, Raingeard de la Bletiere D, Bourreille A, et al. Butytraste inhibits inflammatory responses through NF-κB inhibition: imp lications for Crohn’s disease [J]. Gut, 2000, 47: 397-403.
[15] Muller JM, Ziegler-Heitbrock HW, Baeuerle PA. Nuclear factor kappa B, a mediator of lipopolysaccharide effects [J]. Immunobiology, 1993, 187: 233-256.
[16] Baeuerle PA, Henkel T. Function and activition of NF-kappa B in the immune system [J]. Annu Rev Immunol, 1994, 12: 141-179.
[17] Jobin C, Hekkerbrand C, Licato LL, et al. Mediation by NF-κB of cytokine induced exp ression of intercellular adhesion molecule 1 ( ICAM-1) in an intestinal ep ithelial cell line, a process blocked by proteasome inhibitors [J]. Gut, 1998, 42: 779-787.
[18] Wang LX, Walia B, Evans J, et al. IL-6 induces NF-κB activation in the intestinal epithelia [J]. J Immunol, 2003, 171: 3194-3201.
[19] Jobin C, Herfarth HH, Sartor RB. Dexamethasone inhibits TNF-alpha gene expression through an I kappa B/NF kappa B pathway in intestinal IEC-6 cells [J]. Gastroenterology, 1996, 110: 333-341.
[20] Luhrs H, Gerke T, Muller JG, et al. Butyrate inhibits NF-κB activation in lamina propria macrophages of patientswith ulcerative colitis [J]. Scand J Gastroenterol, 2002, 37: 458-466.