基于弱键诱导的超分子体系探究熊去氧胆酸-小檗碱超分子对溃疡性结肠炎的治疗作用  

Based on the weak-bond induced supramolecular system to explore the therapeutic effect of ursodeoxycholic acid-berberine supramolecular nanoparticles on ulcerative colitis

作　　者：高杉 高丰 孔靖玮 王志家 郑浩呈 蒋欣琪 许书静 李善兰 卢明军 戴子琦 褚福浩[1] 徐冰[1] 雷海民[1] Gao Shan;Gao Feng;Kong Jing-wei;Wang Zhi-jia;Zheng Hao-cheng;Jiang Xin-qi;Xu Shu-jing;Li Shan-lan;Lu Ming-jun;Dai Zi-qi;Chu Fu-hao;Xu Bing;Lei Haimin(School of Chinese Materia Medica,Beijing University of Chinese Medicine,102488,China;School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,102488,China;College of Life Sciences,Beijing University of Traditional Chinese Medicine,102488,China)

机构地区：[1]北京中医药大学中药学院,北京102488 [2]北京中医药大学中医学院,北京102488 [3]北京中医药大学生命科学学院,北京102488

出　　处：《中国中药杂志》2023年第10期2739-2748,共10页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(82274082);北京市高精尖学科-系统中药学项目(2020-JYB-XJSJJ-007);北京中医药大学自然科学类项目(2022-JYB-JBZR-016)。

摘　　要：溃疡性结肠炎是一种反复发作、迁延难愈的炎症性肠病,黄连和牛黄作为清热解毒类中药,一直以来被广泛用于溃疡性结肠炎的治疗。该实验使用黄连的主要活性成分小檗碱和牛黄的主要活性成分熊去氧胆酸通过模拟共煎煮过程得到熊去氧胆酸-小檗碱超分子,以提高两者对溃疡性结肠炎的治疗效果。通过场发射扫描电子显微镜和动态光散射技术进行形貌表征,发现超分子为类四面体型纳米颗粒,平均粒径为180 nm;并结合紫外光谱、荧光发射光谱、红外光谱、高分辨质谱和核磁共振氢谱对其分子结构进行阐述,结果表明该超分子的形成是通过两者之间的相互静电引力作用和疏水作用,此外超分子还存在缓释效果和pH敏感性。采用自由饮用葡聚糖硫酸钠诱导小鼠急性溃疡性结肠炎模型,发现超分子能有效改善结肠炎小鼠的体质量下降和结肠缩短(P<0.001);使疾病活动指数降低(P<0.01),并且超分子组与机械混合物组有明显的统计学差异(P<0.001,P<0.05);通过酶联免疫吸附法(ELISA)测定小鼠血清中的肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6),发现超分子能使血清中TNF-α和IL-6水平显著降低(P<0.001),且与机械混合物组有明显区别(P<0.01,P<0.05);流式细胞术结果提示超分子能显著减少结肠固有层中性粒细胞的募集(P<0.05),且与机械混合物组有较为明显的区别(P<0.05);以上结果说明超分子相比机械混合物组能有效改善小鼠急性溃疡性结肠炎的相关症状。该研究为针对中药小分子吸收性差、治疗效果不理想的情况,提供了新的研究思路,并为中药纳米载药系统研究提供了基础。An inflammatory bowel illness that is recurrent and resistant is ulcerative colitis.As traditional Chinese remedies to remove heat and cleanse,coptis and bezoar have long been used to treat ulcerative colitis.In order to enhance the therapeutic impact with ulcerative colitis,berberine,the primary active component of coptis,and ursodeoxycholic acid,the primary active ingredient of bezoar,were employed to create ursodeoxycholic acid-berberine supramolecule by replicating the co-decocting process.By using field emission scanning electron microscopy and dynamic light scattering,it was discovered that the supramolecule was made up of tetrahedral nanoparticles with an average particle size of 180 nm.The results showed that the formation of the supramolecule was through the mutual electrostatic attraction and hydrophobic interaction between the BBR and UDCA.Additionally,supramolecular had slow release effect and pH senescence.The two-dimensional structure of the supramolecule was described in combination with ultraviolet visible spectroscopy,fluorescence emission spectroscopy,infrared spectroscopy,high resolution mass spectrum,and nuclear magnetic resonance hydrogen spectrum.Supramolecular group improved weight loss,colon shortening of mice(P<0.001),and decrease of disease activity index(P<0.01)with significant statistical difference between supramolecular group and mechanical mixture group(P<0.001,P<0.05),according to the mice model of acute ulcerative colitis that was induced by free drinking of sodium glucan sulfate.Tumor necrosis fact or(TNF)and interleukin-6(IL-6)levels in the serum of mice in the supramolecule group were significantly lower(P<0.001)than those in the mechanical mixture group(P<0.01,P<0.05),as determined by enzyme linked immunosorbent assay(ELISA).According to flow cytometry,supramolecule group was considerably different from mechanical mixture in its ability to dramatically diminish neutrophil recruitment in the lamina propria of the colon(P<0.05).These findings suggested that as compared to the me

关 键 词：超分子 自组装 熊去氧胆酸 小檗碱 溃疡性结肠炎 

分 类 号：R285.5[医药卫生—中药学]