Potential biomarkers found by protein profiling may provide insight for the macrovascular pathogenesis of diabetes mellitus.

Potential biomarkers found by protein profiling may provide insight for the macrovascular pathogenesis of diabetes mellitus.
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DOI:
10.1155/2006/450762
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发表时间:
2006
期刊:
影响因子:
--
通讯作者:
Yue KK
Yue KK
中科院分区:
医学4区
文献类型:
--
作者:
Cho WC;Yip TT;Chung WS;Leung AW;Cheng CH;Yue KK

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糖尿病(DM)是严重威胁人类健康的疾病,其发病机制尚不清楚。本研究的目的是寻找潜在的生物标志物,作为糖尿病发病机制的时间过程指标。根据我们之前的研究结果,氧化应激发生在第8周,我们在注射STZ后的第4、8和12周分别获得102只STZ诱导的糖尿病大鼠和85只对照雄性Sprague-Dawley大鼠的主动脉裂解液和血清。采用表面增强激光解吸/电离飞行时间质谱技术在原子孔灵敏度范围内对蛋白质谱进行了研究。在主动脉中,4周时发现多种生物标志物。第8周发现4个生物标志物,第12周发现3个生物标志物。在血清中发现3个峰和2个生物标志物的三联体在所有时间间隔内均具有100%的分类准确率来区分DM组和对照组。此外,在第12周还发现2个生物标志物具有较高的分类价值。比较糖尿病大鼠和非糖尿病大鼠的主动脉和血清,发现了一束具有显著峰值强度变化和高分类价值的潜在生物标志物。两种血清生物标志物与SWISS-PROT知识库中的胰岛淀粉样蛋白多肽和抵抗素相匹配。使用免疫测定试剂盒进行了验证。这些潜在的生物标志物可能为糖尿病和大血管并发症的发病机制提供有价值的见解。
Diabetes mellitus (DM) is an alarming threat to health of mankind, yet its pathogenesis is unclear. The purpose of this study was to find potential biomarkers to serve as indicators for the pathogenesis of DM in a time course manner. Based on our previous findings that oxidative stress occurred at week 8, aorta lysate and sera of 102 streptozotocin (STZ)-induced diabetic and 85 control male Sprague-Dawley rats were obtained at the 4th, 8th and 12th week after STZ injection. The protein profiles were studied employing surface-enhanced laser desorption/ionization time-of-flight mass spectrometry technology in attomole sensitivity range. In the aorta, a multiple biomarker panel was discovered at the 4th week. At the 8th week, 4 biomarkers were found, while at the 12th week, 3 biomarkers were identified. In the sera, a triplet of 3 peaks and 2 biomarkers were all discovered to have 100% classification accuracy rate to differentiate the DM and control groups at all time intervals. Besides, 2 biomarkers were also found to have high classification value at week 12. Comparing the aorta and sera from DM and non-DM rats, a bundle of potential biomarkers with significant changes in peak intensities and high classification values were found. Two of the serum biomarkers matched with islet amyloid polypeptide and resistin in the SWISS-PROT knowledgebase. Validation has been conducted using immunoassay kits. These potential biomarkers may provide valuable insight on the pathogenesis of DM and macrovascular complications.