Guo Zhi-li, Zhu Yan, Su Xiao-tao, Liu Jun, Yang Qian-xu, Nan Jing-yi, Zhao Bu-chang, Zhang Ying-ying, Yu Ya-nan, Li Bing, Xiao Hong-bin, Wang Zhong
1] Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China [2] Jiaxing Traditional Chinese Medicine Affiliated Hospital of Zhejiang Chinese Medical University, Jiaxing 314000, China.
1] Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China [2] Beijing Electric Power Hospital, Capital Medical University, Beijing 10073, China [3] Xi'an Buchang Pharmaceutical Co, Ltd, Xi'an 712000, China.
Acta Pharmacol Sin. 2015 Jun;36(6):748-57. doi: 10.1038/aps.2014.167. Epub 2015 May 4.
To determine how the relative amino acid contents and metabolic pathways regulate the pharmacological phenotypes in rats with cerebral ischemia after treatment with varying doses of DanHong injection (DHI).
Adult male rats underwent middle cerebral artery occlusion (MCAO), and were injected with DHI (DH-1: 1 mL/kg; DH-2: 2.5 mL/kg; DH-3: 5 mL/kg, and DH-4: 10 mL/kg, iv) daily for 3 d. The neurological deficit score, body weights and infarct volume were assessed. Serum levels of 20 free amino acids were determined using HPLC, and the values were transformed through the quantitative analysis of the amino acids in the serum metabolic spectrum. Multivariate statistical analysis methods (PCA and PLS-DA) and web-based metabolomics tools (MetPa and MetaboAnalyst) were used to analyze the biological data sets for the amino acids.
Administration of DHI dose-dependently decreased cerebral infarct volume, and ameliorated neurological deficits. A total of 5, 6, 7 and 7 non-overlapping metabolites were identified in the DH-1, DH-2, DH-3, and DH-4 groups, respectively. Eight metabolites were shared between the DHI groups and the vehicle group. In addition, the serum levels of glutamic acid, aspartic acid and serine increased with increasing DHI dose. A total of 3, 2, 2 and 5 non-overlapping metabolic pathways were identified in the DH-1, DH-2, DH-3 and DH-4 groups, respectively, and glycine, serine, threonine and histidine metabolism were identified as overlapping pathways among the 4 dose groups.
Overlapping and non-overlapping amino acid metabolites and metabolic pathways are associated with the dose-dependent neuroprotective effect of DHI.
确定不同剂量丹红注射液（DHI）治疗后，大鼠脑缺血时相对氨基酸含量和代谢途径如何调节其药理表型。
成年雄性大鼠进行大脑中动脉闭塞（MCAO）手术，随后每天静脉注射DHI（DH - 1：1 mL/kg；DH - 2：2.5 mL/kg；DH - 3：5 mL/kg；DH - 4：10 mL/kg），连续3天。评估神经功能缺损评分、体重和梗死体积。采用高效液相色谱法测定血清中20种游离氨基酸水平，并通过血清代谢谱中氨基酸的定量分析对数值进行转换。使用多变量统计分析方法（主成分分析和偏最小二乘判别分析）以及基于网络的代谢组学工具（MetPa和MetaboAnalyst）分析氨基酸的生物学数据集。
给予DHI可剂量依赖性地减少脑梗死体积，并改善神经功能缺损。在DH - 1、DH - 2、DH - 3和DH - 4组中分别鉴定出5、6、7和7种非重叠代谢物。DHI组和溶剂对照组共有8种代谢物相同。此外，谷氨酸、天冬氨酸和丝氨酸的血清水平随DHI剂量增加而升高。在DH - 1、DH - 2、DH - 3和DH - 4组中分别鉴定出3、2、2和5条非重叠代谢途径，甘氨酸、丝氨酸、苏氨酸和组氨酸代谢被确定为4个剂量组间的重叠途径。
重叠和非重叠的氨基酸代谢物及代谢途径与DHI的剂量依赖性神经保护作用相关。
