中文摘要
基于丁桂散脐部给药对大鼠寒证溃疡性结肠炎(UC)的特异性作用,及小分子透明质酸(HA)修饰甘油醇质体(GLY/LS)新型载体(HA-GLY/LS)的穴区深层皮肤靶向性能,结合基因组学及肠动力学探索UC发病机制与治疗作用的研究进展,本课题拟探讨载丁桂散HA-GLY/LS脐部给药散寒止痛的效应机制。首先考察HA-GLY/LS递药系统在穴区与旁开皮肤的吸收性能;分析脐部给药对各种递质,与胃肠动力调节关键细胞-Cajal间质细胞数量与功能的影响。继之,观察脐部给药对结肠microRNA表达谱及甲基化DNA谱的影响,筛选差异化基因。最后,对差异化microRNA/甲基化DNA进行联合分析,结合结肠动力学考察结果,阐释丁桂散脐部给药特异性作用的靶基因与作用通路。从而验证“丁桂散脐部给药后,通过调控结肠microRNA靶基因,和/或调控肠道动力学特殊通道,发挥经穴给药特异性效应”的科学假说。
英文摘要
The purpose of this project was to investigate the the mechanism of action of the special eliminating cold to stop pain effect of Dinggui-loaded HA-GLY/LS by administration on umbilical skin area, according to the specific effect of umbilical administration of Dinggui San to rats on cold syndrome ulcerative colitis (UC), and using small molecule hyaluronic acid (HA) modified glycerol-ethosomes (GLY/LS) as new carrier (HA-GLY/LS) targeting to deeper layers of acupoint skin area, combining research advances of intestinal dynamics and Genome on UC pathogenesis and therapeutic effects. Firstly, the skin absorption of drug delivered by HA-GLY/LS through umbilical administration was evaluated. Secondly, various neurotransmitters were analyzed after umbilical administration, and the the function gastrointestinal motility regulators on Cajal interstitial cells was also evaluated. Followed by observation umbilical administration on colon microRNA expression profiling and DNA methylation profiles, screening differentiation genes. So, the target genes and Pathway of the special effects of Dinggui San umbilical administration can be interpreted from the difference microRNA/DNA methylation analysis and combined with the colon dynamics study results. Thereby, the hypothesis "The specific therapeutic effect Dinggui San by umbilical administration can be achieved through colon microRNA target gene regulation and / or regulation of intestinal motility special channel ". The mechanism of the umbilical administration can be interpreted, which may also promote developing novel transdermal drug delivery system for administration on acupoint skin area, and improve the level of basic research of traditional Chinese medicine.
