马齿苋-肉桂颗粒剂制备及对溃疡性结肠炎小鼠肠道菌群的影响
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摘要
目的研究马齿苋-肉桂颗粒剂制备工艺及其对溃疡性结肠炎(UC)模型小鼠肠道菌群的影响。方法蔗糖为辅料,膏料比按1∶2、1∶3、1∶4和1∶5制备颗粒,从外观性状、溶化性和粒度三方面对颗粒进行质量检查,从颗粒粘度、粒径和pH三方面对颗粒溶液及稀释液的物理化学参数进行考察;用5%葡聚糖硫酸钠(DSS)诱导小鼠UC模型,灌胃125mg/kg柳氮磺胺吡啶为阳性对照,给药组分别灌胃各膏辅比颗粒溶液,观察小鼠给药前后的体症,进行疾病活动指数评分(DAI),并观察结肠组织形态、肠道菌群整体轮廓和菌群生物多样性的变化以及进行菌群物种注释及差异分析。结果综合物理化学参数测定结果和颗粒剂评价结果,膏辅比1∶3所制得颗粒各项参数较其他配比表现良好;给药治疗UC小鼠后,DAI评分表明小鼠体症有所改善,HE染色显示小鼠结肠黏膜上皮溃疡处有不同程度修复;肠道菌群轮廓和菌群生物多样性的变化以及菌群物种注释及差异分析结果说明给药后能一定程度上促进肠道菌群结构的恢复,药物可能通过促进肠道菌群结构的恢复从而减轻肠道炎症,LefSe分析结果显示双歧杆菌科的一些菌群对UC小鼠肠道菌群有调节作用。结论获得马齿苋-肉桂颗粒剂制备的最佳膏辅比。给药治疗UC小鼠后,从DAI、HE染色、肠道菌群变化方面得出马齿苋-肉桂颗粒剂对UC小鼠肠道菌群有一定的影响,为临床治疗UC提供了新思路。
Objective To study the preparation process of purslane-cinnamon granules and its effect on intestinal flora of mice with ulcerative colitis(UC).Methods Sucrose was used as the excipient to prepare the granules,with the ratios of paste to excipient of 1∶2,1∶3,1∶4 and 1∶5 respectively.Quality control was performed with the respect of the appearance of characters,melting and particle size.The physicochemical parameters of the solutions and dilutions of the granules including the granule viscosity,particle size and pH were determined.The mouse models of UC were induced with 5% dextran sulfate(DSS);positive controls were established by giving 125 mg/kg sulfasalazine by gavage.The administration group was given the solutions of granules with different ratios of paste to excipient,and the signs and symptoms of mice were observed before and after drug administration.The disease activity index(DAI)was evaluated,and the mor-phology of colonic tissue,the overall profile of intestinal flora and the variation of microbial diversity were observed;the species and difference of flora were analyzed.Results The granules with the ratio of paste to excipient of 1∶3 revealed better comprehensive physicochemical parameters than those with other ratios.After administration of the drug,the signs and symptoms of the mice were improved;the ulcer in the epithelial mucosa of mouse colon were repaired in different degrees.The floral species and difference analysis showed improvement of the construction of intestinal flora and relief of intestinal inflammation.The results of LefSe analysis showed that some Bifidobacteria had regulatory effects on intestinal flora of UC mice.Conclusion The optimal ratio of paste to excipient of the purslane-cinnamon granules was obtained.The granules have certain effects on the intestinal flora of UC mice,which provides a new way for clinical treatment of UC.
Objective To study the preparation process of purslane-cinnamon granules and its effect on intestinal flora of mice with ulcerative colitis(UC).Methods Sucrose was used as the excipient to prepare the granules,with the ratios of paste to excipient of 1∶2,1∶3,1∶4 and 1∶5 respectively.Quality control was performed with the respect of the appearance of characters,melting and particle size.The physicochemical parameters of the solutions and dilutions of the granules including the granule viscosity,particle size and pH were determined.The mouse models of UC were induced with 5% dextran sulfate(DSS);positive controls were established by giving 125 mg/kg sulfasalazine by gavage.The administration group was given the solutions of granules with different ratios of paste to excipient,and the signs and symptoms of mice were observed before and after drug administration.The disease activity index(DAI)was evaluated,and the mor-phology of colonic tissue,the overall profile of intestinal flora and the variation of microbial diversity were observed;the species and difference of flora were analyzed.Results The granules with the ratio of paste to excipient of 1∶3 revealed better comprehensive physicochemical parameters than those with other ratios.After administration of the drug,the signs and symptoms of the mice were improved;the ulcer in the epithelial mucosa of mouse colon were repaired in different degrees.The floral species and difference analysis showed improvement of the construction of intestinal flora and relief of intestinal inflammation.The results of LefSe analysis showed that some Bifidobacteria had regulatory effects on intestinal flora of UC mice.Conclusion The optimal ratio of paste to excipient of the purslane-cinnamon granules was obtained.The granules have certain effects on the intestinal flora of UC mice,which provides a new way for clinical treatment of UC.
引文
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[10]WEI Yongkai,GENG Funeng,ZHAO Wei,et al.Therapeutic effects and immunization of mesalazine and SASP on active ulcerative colitis model of Balb/c mice induced by DSS[J].Chin J Hosp Pharmacy,2016,36(14):1190-1195.(in Chinese)魏永凯,耿福能,赵微,等.美沙拉嗪、柳氮磺胺吡啶对葡聚糖硫酸钠诱导的Balb/c小鼠急性溃疡性结肠炎的治疗和免疫影响[J].中国医院药学杂志,2016,36(14):1190-1195.
[11]乔竹稳,姚旭颖,单喜臣,等.马齿苋化学成分研究[J].齐齐哈尔大学学报(自然科学版),2012,28(1):58-60.
[12]ZHAO Kai,XUE Peifeng,TU Pengfei,et al.Research progress of chemical constituents and pharmacological activities of cinnamon[J].J Inner Mongolia Med Univ,2013,35(1):63-74.(in Chinese)赵凯,薛培凤,屠鹏飞,等.肉桂的化学成分及其生物活性研究进展[J].内蒙古医科大学学报,2013,35(1):63-74.
[13]刘亚静,张仲.中药肉桂的药理作用研究进展[J].现代中西医结合杂志,2011,20(23):2989-2990.
[14]FENG Lan,LI Shaomin,DAI Lijuan,et al.Effects of polysaccharides from Portulaca oleracea L.on intestinal mucosal cytokines and intestinal flora in mice with ulcerative colitis[J].Chin J Microecol,2015,27(2):139-142.(in Chinese)冯澜,李绍民,代立娟,等.马齿苋多糖对溃疡性结肠炎小鼠肠黏膜细胞因子及肠道菌群的影响[J].中国微生态学杂志,2015,27(2):139-142.
[2]Wang YF,Ouyang Q,Hu RW.Progression of inflammatory bowel disease in China[J].J Digest Dis,2010,11(2):76-82.
[3]Borody TJ,Campbell J.Fecal microbiota transplantation:Current status and future directions[J].Expert Rev Gastroenterol Hepatol,2011,5(6):653-655.
[4]Ordás I,Eckmann L,Talamini M,et al.Ulcerative colitis[J].Lancet,2012,380(9853):1606-1619.
[5]DAI Guoliang,ZHU Lijing,ZONG Yang,et al.Preparation technology and quality standard of herbaceous peony Granules[J].JAnhui Sci Technol Univ,2016,30(4):31-34.(in Chinese)戴国梁,朱立静,宗阳,等.芍药颗粒剂制备工艺及质量标准[J].安徽科技学院学报,2016,30(4):31-34.
[6]ZHOU Zheng,MA Ting,FENG Lan,et al.Effects of polysaccharides fromPortulaca oleracea L.on intestinal flora and blood endotoxin in mice with ulcerative colitis[J].Chin J Microecol,2014,26(6):646-648.(in Chinese)周正,马婷,冯澜,等.马齿苋多糖对溃疡性结肠炎小鼠肠道菌群及血内毒素的影响[J].中国微生态学杂志,2014,26(6):646-648.
[7]Murano M,Maemura K,Hirata I,et al.Therapeutic effect of intracolonically administered nuclear factor kappa B(p65)antisense oligonucleotide on mouse dextran sulphate sodium(DSS)-induced colitis[J].Clin Exp Immunol,2000,120(1):51-58.
[8]Sánchez-Fidalgo S,Cárdeno A,Sánchez-Hidalgo M,et al.Dietary extra virgin olive oil polyphenols supplementation modulates DSS-induced chronic colitis in mice[J].J Nutr Biochem,2013,24(7):1401-1413.
[9]KONG Pengfei,ZHAO Bing,QIN Qin et al.The establishment and evaluation of acute ulcerative colitis in rat model induced with DSS[J].Chin J Colorec Dis(Electronic),2015,4(6):617-619.(in Chinese)孔鹏飞,赵兵,覃勤,等.葡聚糖硫酸钠致大鼠急性溃疡性结肠炎模型建立与评价[J].中华结直肠疾病电子杂志,2015,4(6):617-619.
[10]WEI Yongkai,GENG Funeng,ZHAO Wei,et al.Therapeutic effects and immunization of mesalazine and SASP on active ulcerative colitis model of Balb/c mice induced by DSS[J].Chin J Hosp Pharmacy,2016,36(14):1190-1195.(in Chinese)魏永凯,耿福能,赵微,等.美沙拉嗪、柳氮磺胺吡啶对葡聚糖硫酸钠诱导的Balb/c小鼠急性溃疡性结肠炎的治疗和免疫影响[J].中国医院药学杂志,2016,36(14):1190-1195.
[11]乔竹稳,姚旭颖,单喜臣,等.马齿苋化学成分研究[J].齐齐哈尔大学学报(自然科学版),2012,28(1):58-60.
[12]ZHAO Kai,XUE Peifeng,TU Pengfei,et al.Research progress of chemical constituents and pharmacological activities of cinnamon[J].J Inner Mongolia Med Univ,2013,35(1):63-74.(in Chinese)赵凯,薛培凤,屠鹏飞,等.肉桂的化学成分及其生物活性研究进展[J].内蒙古医科大学学报,2013,35(1):63-74.
[13]刘亚静,张仲.中药肉桂的药理作用研究进展[J].现代中西医结合杂志,2011,20(23):2989-2990.
[14]FENG Lan,LI Shaomin,DAI Lijuan,et al.Effects of polysaccharides from Portulaca oleracea L.on intestinal mucosal cytokines and intestinal flora in mice with ulcerative colitis[J].Chin J Microecol,2015,27(2):139-142.(in Chinese)冯澜,李绍民,代立娟,等.马齿苋多糖对溃疡性结肠炎小鼠肠黏膜细胞因子及肠道菌群的影响[J].中国微生态学杂志,2015,27(2):139-142.