细菌性脑膜炎大鼠模型的尿液蛋白质组学变化

Changes of urinary proteins in a bacterial meningitis rat model

摘要:

与脑脊液和血液不同，尿液不受到稳态机制的调节，更倾向于积累和反应机体生理和病理状态下的变化。生物标志物的本质特征是变化，因此尿液是寻找疾病早期标志物的更好来源。在世界范围内，细菌性脑膜炎依然是引起新生儿和儿童疾病的主要原因。为了降低死亡率和致残率，需要用无创的方法寻找细菌性脑膜炎的相关线索。本研究中，使用大鼠脑室内注射大肠杆菌模型模拟细菌性脑膜炎，在第1天和第3天的大鼠尿液中寻找尿液蛋白谱的差异变化，为进一步寻找大肠杆菌性脑膜炎的早期生物标记物研究进行初步的探索。通过膜上酶切和胶内酶切将尿蛋白切成肽段并通过液相色谱串联质谱技术 (LC-MS/MS) 分析肽段信息。第1天的尿液通过胶内酶切方法鉴定到17个差异蛋白，通过膜上酶切鉴定到20个差异蛋白；第3天的尿液通过膜上酶切方法鉴定到5个差异蛋白。这些差异蛋白为寻找细菌性脑膜炎早期生物标志物的初步探索奠定了基础。

Abstract:

Unlike cerebrospinal fluid or blood, urine accumulates metabolic changes of the body and has the potential to be a promising source of early biomarkers discovery. Bacterial meningitis is a major cause of illness among neonates and children worldwide. In this study, we used Escherichia coli-injected rat model to mimic meningitis and collected urine samples on day 1 and day 3. We used two different methods to digest proteins and analyzed peptides by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We identified 17 and 20 differential proteins by two methods respectively on day 1, and 5 differential proteins by filter-aided digestion method on day 3. Finding these differential proteins laid a foundation to further explore biomarkers of bacterial meningitis.