药学学报, 2021, 56(10): 2841-2848
引用本文:
丁琅, 张昕, 李芹英, 王晨, 尚庆森, 蔡超, 李国云, 于广利. 基于液相色谱-质谱联用技术的2型糖尿病小鼠皮肤中糖胺聚糖表达谱分析[J]. 药学学报, 2021, 56(10): 2841-2848.
DING Lang, ZHANG Xin, LI Qin-ying, WANG Chen, SHANG Qing-sen, CAI Chao, LI Guo-yun, YU Guang-li. Expression profiling of glycosaminoglycans in the skin of type 2 diabetic mice based on liquid chromatography-mass spectrometry[J]. Acta Pharmaceutica Sinica, 2021, 56(10): 2841-2848.

基于液相色谱-质谱联用技术的2型糖尿病小鼠皮肤中糖胺聚糖表达谱分析
丁琅1, 张昕1, 李芹英1, 王晨1, 尚庆森1,2, 蔡超1,2, 李国云1,2*, 于广利1,2*
1. 中国海洋大学医药学院, 山东省糖科学与糖工程重点实验室, 海洋药物教育部重点实验室, 山东 青岛 266003;
2. 海洋药物与生物制品实验室, 青岛海洋科学与技术试点国家实验室, 山东 青岛 266237
摘要:
2型糖尿病是一种常见的糖尿病,对于糖尿病患者而言,由于身体机能受损导致其伤口不能正常愈合,可能引起严重后果。糖胺聚糖(GAGs)广泛存在于皮肤组织中,由于其糖醛酸C6异构化和不同硫酸基取代,GAGs的结构较为复杂,目前尚未对糖尿病患者皮肤中GAGs的精细结构进行研究。本研究通过液相-质谱联用技术(LC-MS/MS)对链脲佐菌素(STZ)诱导2型糖尿病小鼠皮肤中GAGs精细结构进行表征。动物实验操作均遵循中国海洋大学动物伦理委员会的规定。结果表明,STZ-诱导型糖尿病小鼠皮肤中透明质酸(HA)含量显著低于正常组。糖尿病小鼠皮肤中硫酸软骨素(CS)和硫酸乙酰肝素(HS)含量与正常组虽然没有显著性差异,但是其二糖精细结构含量存在差异。糖尿病小鼠皮肤中CS-4S6S、HS-0S、HS-NS和HS-6S等二糖的表达均显著增多,HS-NS6S显著减少,另外,其HS的硫酸化程度也显著低于正常组。这些结果为糖尿病的病理机制的阐明及糖尿病患者伤口愈合敷料的开发提供了依据。
关键词:    糖尿病      糖胺聚糖      液相色谱-质谱法      皮肤     
Expression profiling of glycosaminoglycans in the skin of type 2 diabetic mice based on liquid chromatography-mass spectrometry
DING Lang1, ZHANG Xin1, LI Qin-ying1, WANG Chen1, SHANG Qing-sen1,2, CAI Chao1,2, LI Guo-yun1,2*, YU Guang-li1,2*
1. Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China;
2. Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China
Abstract:
Type 2 diabetes is a common form of diabetes and can have serious consequences for diabetics when their wounds do not heal properly due to impaired function. Glycosaminoglycans (GAGs) are widely found in skin tissue. Due to the isomerization of C6 in uronic acid and different sulfuric acid substitutions, the structure of GAGs is relatively complex. The fine structure of GAGs in the skin of diabetic patients has not been studied. In this study, the structure of GAGs in the skin of streptozotocin (STZ)-induced diabetic mice was characterized by liquid chromatographytandem mass spectrometry (LC-MS/MS). All animal experiments were carried out with approval of the Animal Ethics Committee of Ocean University of China. The results indicate that the content of hyaluronic acid (HA) in STZ-induced diabetic mouse skin was significantly lower than that of non-diabetic mice. Although there was no significant difference in the content of chondroitin sulfate (CS) and heparin sulfate (HS) between diabetic mouse and normal mouse skin, the disaccharide compositions were different. The expression of CS-4S6S, HS-0S, HS-NS, and HS-6S in STZ-induced diabetic mouse skin was higher than in non-diabetic mice. While the content of HS-NS6S was lower. In addition, the degree of sulfation of HS in STZ-induced mouse skin was lower than that of normal mouse skin. These results provide a basis for the pathogenesis of diabetes and the development of wound healing dressings for diabetic patients.
Key words:    diabetes    glycosaminoglycan    liquid chromatography-mass spectrometry    skin   
收稿日期: 2021-04-01
DOI: 10.16438/j.0513-4870.2021-0476
基金项目: 国家自然科学基金资助项目(31600646,81991522);国家新药创制科技重大专项(2018ZX09735004);泰山学者攀登计划(TSPD20210304).
通讯作者: 李国云,Tel/Fax:86-532-8203-1615,E-mail:liguoyun@ouc.edu.cn;于广利,E-mail:glyu@ouc.edu.cn
Email: liguoyun@ouc.edu.cn;glyu@ouc.edu.cn
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