中文摘要
在课题组前期大量临床与基础研究证实针灸能有效控制或缓解克罗恩病(Crohn’s disease,CD)肠道炎症和调节免疫异常的基础上,结合目前国际前沿“自噬异常是导致CD发生与发展的重要环节之一”理论认识,采用分子生物学与表观遗传学相关技术,结合生物信息学分析,以染色质重塑相关酶及组蛋白H3赖氨酸修饰所调控的自噬相关靶基因转录与表达异常为切入点,拟从临床与动物研究二方面证实:针灸调节CD自噬效应可能是通过调节CD染色质重塑相关酶Brg1、LSD1、HDACs、hMOF的异常表达,继而调控组蛋白H3K27me3、H3K4me2和H3K27ac修饰水平,影响其在自噬相关靶基因增强子或启动子区域的富集,由此调控自噬相关基因/因子ATG16L1、IRGM、IL-18的转录与表达,初步阐明针灸调节染色质重塑介导的CD自噬的表观遗传调控机制,以期为深入揭示针灸治疗CD的效应机制提供科学依据和理论基础。
英文摘要
Based on a large number of the previous clinical and basic studies,which are confirmed that acupuncture and moxibustion can effectively control or decrease intestinal inflammatory and regulate the abnormal immunity in Crohn's disease (CD). Combined with the current international frontier theory that autophagy abnormalities is one of the important links during the occurrence and development of CD. The reseach will adopt the related technologies of molecular biology and epigenetics, use the bioinformatics analysis, and start the research from the point of autophagy gene transcriptions and abnormal expressions regulated by chromatin remodeling-related enzymes and histone H3 lysine modification. It intend to confirm from clinical and animal studies that: acupuncture and moxibustion may affect autophagy of CD by regulating the abnormal expressions of chromatin remodeling-related enzymes Brg1, LSD1, HDACs and hMOF, thus regulate the modification levels of H3K27me3, H3K4me2 and H3K27ac, and then affect the concentrations in autophagy-related target genes enhancer or promoter region, thereby regulate the expressions and transcriptions of autophagy-related genes and factors ATG16L1, IRGM and IL-18. Aim to clarify preliminarily the epigenetic regulatory mechanisms of acupuncture and moxibustion regulating CD autophagy mediated by chromatin remodeling, and provide the scientific and theoretical bases for further revealing the effect mechanism of acupuncture and moxibustion on CD.
