化学学报 ›› 2011, Vol. 69 ›› Issue (19): 2265-2271. 上一篇    下一篇

研究论文

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

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   

  1. (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)
  • 投稿日期:2010-11-28 修回日期:2011-06-02 发布日期:2011-06-21
  • 通讯作者: 谢丽云 E-mail:437655792@qq.com
  • 基金资助:

    国家自然科学基金;浙江省医药卫生专项

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

Xie Liyun1 Song Caiyong1 Lou Yiyi 1 Xu Zhi 1 Zhang Meiling1 Dong Baijun2 Gao Hongchang*,1 Li Xiaokun1   

  1. (1 School of Pharmacy, Wenzhou Medical College, Wenzhou 325035)
    (2 School of Medicine, Shanghai Jiao Tong University, Shanghai 200127)
  • Received:2010-11-28 Revised:2011-06-02 Published:2011-06-21

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.

关键词: 糖尿病溃疡, 1H NMR, 病理机制, 皮肤组织

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.

Key words: diabetic ulcer, 1H NMR, pathological mechanisms, skin tissue

中图分类号: