基于~1H NMR代谢组学方法的糖尿病溃疡组织代谢特征和病理机制分析  

Studies on Metabolic Characteristics and Pathological Mechanisms of Diabetic Ulcers by ~1H NMR-based Metabonomics

作　　者：谢丽云[1] 宋才勇[1] 娄依依[1] 徐志[1] 张美玲[1] 董柏君[2] 高红昌[1] 李校堃[1] 

机构地区：[1]温州医学院药学院,温州325035 [2]上海交通大学医学院附属仁济医院泌尿科,上海200127

出　　处：《化学学报》2011年第19期2265-2271,共7页Acta Chimica Sinica

基　　金：国家自然科学基金(Nos.21175099;30872961);浙江省医药卫生专项(No.2010QNA016)资助项目

摘　　要：糖尿病溃疡是临床上导致患者截肢的最主要原因,应用基于1H NMR的代谢组学方法研究了链脲佐菌素(STZ)诱导的SD糖尿病大鼠溃疡组织的代谢轮廓,同时结合组织病理和生化分析,阐述了糖尿病溃疡组织的代谢特征和病理机制.结果表明,糖尿病大鼠在溃疡组织愈合过程中的成纤维细胞增殖和毛细血管增生都明显弱于对照组;代谢组学分析的散点图表明糖尿病溃疡组和对照组在代谢模式上明显分开,不同愈合时间的糖尿病溃疡组在代谢模式上明显分开;载荷图表明糖尿病溃疡组相对于对照组,亮氨酸、异亮氨酸、丙氨酸、柠檬酸、胆碱和甜菜碱等代谢成分含量降低;而乳酸、醋酸、丙酮酸、肌酸、牛磺酸和甘氨酸等代谢成分含量上升.代谢组学提示的代谢物变化表明糖尿病溃疡组织的三羧酸循环被抑制,能量代谢平衡被破坏,溃疡组织可能通过增加无氧酵解和肌酸代谢来维持自身的能量平衡,并自我修复创伤的皮肤组织.本工作的研究有望为糖尿病溃疡的深入认识和治疗方案选择提供参考.Diabetic ulcer is the most important factor leading to clinical amputation.In the present study, 1H NMR-based metabonomics combined with pathological and biochemical analysis were used to study the metabolic characteristics and pathological mechanisms of diabetic ulcers.The results showed that the fibroblast and blood capillaries proliferation in skin ulcers of diabetic rats were significantly weaker than those in the control rats.From the scores plots of metabonomic studies,we found distinct,easily detectable differences between（a） diabetic ulcer rats and control rats,and（b） diabetic ulcer rats with different healing time.Compared to control skin ulcers,diabetic skin ulcers had lower levels of leucine,isoleucine,alanine, citrate,choline and betaine,together with higher levels of lactate,acetate,pyruvate,creatine,taurine and glycine.Altered metabolite concentrations are most likely the result of the cells switching to glycolysis and creatine metabolism to maintain energy homeostasis following the loss of ATP caused by impaired TCA cycle in diabetic ulcers and to repair the skin trauma.The present study may be able to assist deeply understanding of diabetic ulcers and selection of treatment protocols.

关 键 词：糖尿病溃疡 1H NMR 病理机制 皮肤组织 

分 类 号：R587.1[医药卫生—内分泌] R632.1[医药卫生—内科学]