Abstract：OBJECTIVE To find disease biomarkers of cerebral ischemia by establishing cerebral ischemia-reperfusion injury model of rats and comparing with healthy rats. METHODS Cerebral ischemia-reperfusion model of rats was established by modified Longa′s intraluminal suture method. After 24 h of modeling, plasma and brain tissue from the model group and the control group were collected for plasma biochemical indicators and metabolites analysis. Brain slices and plasma biochemical indicators were used to demonstrate the successful modeling. Gas chromatography-mass spectrometry was adopted to conduct targeted metabolomics studies on free fatty acids in rat plasma, tridecanoic acid (C13∶0) and 2,6-di-tert-butyl-4-methylphenol (BHT) were added as internal standard and antioxidant during sample preparation. Methylation was carried out using concentrated sulfuric acid/CH3OH as a derivatization reagent, and a non-polar stationary phase column was selected for chromatographic separation. RESULTS Comparing the model group with the blank group, four differential metabolites were obtained, namely palmitic acid, stearic acid, oleic acid and linoleic acid, which were up-regulated throughout the metabolic pathway. The RESULTS of the relevant metabolic pathway analysis showed that the linoleic acid metabolic pathway had significant changes in the disease process. CONCLUSION In the fatty acid anabolic pathway, the linoleic acid metabolic pathway changes significantly during the onset and treatment of cerebral ischemia-reperfusion. The effect of preventing and treating cerebral ischemia-reperfusion injury can be achieved by controlling the level of linoleic acid. This study evaluates the prognosis of cerebral ischemia reperfusion injury by measuring the plasma of model rats, explores its cause and pathogenesis, and laid a foundation for the study of disease pathology and the mechanism of drug action.
张铭洋, 韩克非, 李清, 刘然. 基于游离脂肪酸靶向脂质组学的脑缺血再灌注血浆生物标志物的筛选[J]. 中国药学杂志, 2020, 55(2): 111-115.
ZHANG Ming-yang, HAN Ke-fei, LI Qing, LIU Ran. Screening of Plasma Biomarkers for Cerebral Ischemia-Reperfusion Based on Free Fatty Acid Targeted Lipidomics. Chinese Pharmaceutical Journal, 2020, 55(2): 111-115.
NICHOLSON J K, CONNELLY J, LINDON J C, et al. Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Dis, 2002,1(2):153-161.
[2]
GUOWANG X, XIN L, SHENGLI Y. Recent Advances in Metabonomics. Acta Acad Med Sin(中国医学科学院学报), 2007,29:701-711.
[3]
NICHOLSON J K, LINDON J C. Systems biology: metabonomics. Nature, 2008, 455(7216):1054-1056.
[4]
WENK M R. Erratum: the emerging field of lipidomics. Nat Rev Drug Dis, 2005, 4: 594-610.
[5]
YANG Z, WEIAN C, SUSU H, et al. Protective effects of mangiferin on cerebral ischemia-reperfusion injury and its mechanisms. Eur J Pharmacol, 2016,771:145-151.
[6]
LONGA E Z, WEINSTEIN P R, CARLSON S, et al. Reversible middle cerebralartery occlusion without craniectomy in rats. Stroke, 1989, 20(1):84-91.
[7]
YAN R, YU H, LAN C, et al. Protection mechanism of the main active ingredients combination of yangyin tongnao granules on cerebral ischemia/reperfusion injury rats. Chin Pharm J(中国药学杂志),2018,53(3):199-204.
2020, Vol. 55 
