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  • 余嘉惠,刘继勇,岳小强.白术黄连方对三硝基苯磺酸诱导溃疡性结肠炎模型大鼠的治疗作用[J].第二军医大学学报,2018,39(2):171-176    [点击复制]
  • YU Jia-hui,LIU Ji-yong,YUE Xiao-qiang.Therapeutic effects of Baizhu Huanglian Decoction on ulcerative colitis in rats[J].Acad J Sec Mil Med Univ,2018,39(2):171-176   [点击复制]
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白术黄连方对三硝基苯磺酸诱导溃疡性结肠炎模型大鼠的治疗作用
余嘉惠1,刘继勇2,岳小强1*
0
(1. 第二军医大学长征医院中医科, 上海 200003;
2. 第二军医大学长海医院药学部, 上海 200433
*通信作者)
摘要:
目的 探讨白术黄连方对三硝基苯磺酸(TNBS)诱导的溃疡性结肠炎(UC)模型大鼠的治疗作用及其机制。方法 取SD大鼠,采用TNBS灌肠法制作大鼠UC模型。将74只大鼠随机分为6组,雌雄各半,由于造模第2天时模型组、柳氮磺胺吡啶组各有1只大鼠死亡,故模型组共13只大鼠,白术黄连方低、中、高剂量组和正常对照组各12只,柳氮磺胺吡啶组11只。白术黄连方低、中、高剂量组造模后分别灌胃给予白术黄连汤剂6.895、13.790、27.580 g/kg,2次/d,2 mL/次;柳氮磺胺吡啶组造模后灌胃给予柳氮磺胺吡啶混悬液0.2 g/kg(2次/d,2 mL/次);模型组造模后给予等量生理盐水;正常对照组始终给予生理盐水。连续给药10 d,观察大鼠体质量、大便情况。给药结束后取结肠检测大鼠结肠病变情况,测量结直肠长度,评估结肠病理及结肠黏膜损伤指数(CMDI)评分,并用ELISA检测大鼠结肠组织一氧化氮(NO)、诱导型一氧化氮合酶(iNOS)、髓过氧化物酶(MPO)、白细胞介素6(IL-6)水平。结果 给药后第4~10天白术黄连方低、中、高剂量组和柳氮磺胺吡啶组大鼠体质量均高于模型组(P均<0.05),而与正常对照组相比差异无统计学意义;白术黄连方高剂量组和柳氮磺胺吡啶组大鼠大便性状评分低于模型组和白术黄连方低、中剂量组,但差异均无统计学意义。白术黄连方中、高剂量组和柳氮磺胺吡啶组大鼠结直肠长度均长于模型组(P均<0.05),白术黄连方低、中、高剂量组和柳氮磺胺吡啶组结肠病理评分均低于模型组(P均<0.05);白术黄连方高剂量组和柳氮磺胺吡啶组大鼠结肠CMDI评分均低于模型组(P均<0.05)。白术黄连方低、中、高剂量组和柳氮磺胺吡啶组大鼠结肠组织NO、iNOS、MPO、IL-6水平均低于模型组(P均<0.05)。结论 白术黄连方能改善TNBS诱导UC模型大鼠的一般情况和结肠病变程度,同时降低肠组织中NO、iNOS、MPO、IL-6的表达,减轻炎症程度。
关键词:  溃疡性结肠炎  白术黄连方  一氧化氮合酶  髓过氧化物酶  白细胞介素6  动物实验
DOI:10.16781/j.0258-879x.2018.02.0171
投稿时间:2017-08-26修订日期:2017-12-26
基金项目:上海市科学技术委员会科研计划项目(15401900600).
Therapeutic effects of Baizhu Huanglian Decoction on ulcerative colitis in rats
YU Jia-hui1,LIU Ji-yong2,YUE Xiao-qiang1*
(1. Department of Traditional Chinese Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China;
2. Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
*Corresponding author)
Abstract:
Objective To explore the therapeutic effects of Baizhu Huanglian Decoction on rats with ulcerative colitis (UC) induced by trinitrobenzene sulfonic acid (TNBS). Methods SD rats were used to make rat UC model by TNBS enema. A total of 74 rats were divided into 6 groups with half of each group being male. Model group had 14 rats, and Baizhu Huanglian Decoction low-, middle-and high-dose groups, control group and sulfasalazine group had 12 rats in each group. One rat in the model group and one in the sulfasalazine group were dead on the 2nd day of modeling. After modeling, the rats of Baizhu Huanglian Decoction low-, middle-and high-dose group were intragastrically given (2 times a day, each time with 2 mL) Baizhu Huanglian Decoction of 6.895, 13.790 and 27.580 g/kg, respectively. Sulfasalazine group was given sulfasalazine suspension by gavage 0.2 g/kg (2 times a day, each time with 2 mL) and model group was given the same amount of normal saline after modeling. Normal control group was always given normal saline. After 10 days of continuous administration, the body mass and fecal characteristics of the rats were observed. At the end of the administration, the colonic pathological changes of colon and the length of colorectal were measured. The colon pathology and colon mucosal injury index (CMDI) score were evaluated. The levels of nitric oxide (NO), inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO) and interleukin-6 (IL-6) were measured by ELISA. Results Compared with the model group, the body mass of the rats were significantly increased on the 4th-10th day after administration in the Baizhu Huanliang Decoction low-, middle-and high-dose groups and sulfasalazine group (all P<0.05), which had no significant difference versus normal control group. Fecal characteristic scores of the Baizhu Huanglian Decoction high-dose groups and the sulfasalazine group were lower than those of the model group and the Baizhu Huanglian Decoction middle-and low-dose groups, but the differences were not statistically significant. Compared with the model group, the colorectal lengths of the rats were significantly longer in Baizhu Huanglian Decoction middle-and high-dose groups and sulfasalzine group (all P<0.05). The colon pathology scores were significantly lower in the Baizhu Huanglian Decoction low-, middle-and high-dose group, and sulfasalazine group versus the model group (all P<0.05). CMDI scores of Baizhu Huanglian Decoction high-dose group and sulfasalazine group were significantly lower than those of the model group (both P<0.05). The levels of NO, iNOS, MPO and IL-6 of the rat colonic tissues were significantly lower in Baizhu Huanliang Decoction low-, middle-and high-dose groups, and sulfasalazine group than those in the model group (all P<0.05). Conclusion Baizhu Huanglian Decoction can improve the general condition and colonic lesions of rats with UC, decreasing the levels of NO, iNOS, MPO and IL-6 and reducing the inflammation.
Key words:  ulcerative colitis  Baizhu Huanglian Decoction  nitric oxide synthase  myeloperoxidase  interleukin-6  animal experiment