OBJECTIVE: To examine the neuroprotective effect of extract from Naomaitong following focal cerebral ischemia reperfusion induced by occlusion of middle cerebral artery(MCA), and to determine the biochemical alteratio...OBJECTIVE: To examine the neuroprotective effect of extract from Naomaitong following focal cerebral ischemia reperfusion induced by occlusion of middle cerebral artery(MCA), and to determine the biochemical alterations in urine using proton nuclear magnetic resonance spectroscopy and principal component analysis.METHODS: Wistar rats were randomly assigned tothree groups: sham-operated group, MCA focal cerebral ischemia reperfusion model group, and active extract of Naomaitong treatment group. The model was established by an improved MCA occlusion(MCAO) method. Sham-operated rats received the same surgical procedure, but without occlusion. The Naomaitong treatment group were treated with active extract from Naomaitong at a dose of3.0 g·kg-·1d-1. Brain tissues and urine samples were collected from all groups for histopathological assessment and proton nuclear magnetic resonance spectroscopy-based metabonomics, respectively.RESULTS: Hematoxylin-eosin and triphenyl tetrazolium chloride staining of brain tissues showed a significant decrease in cerebral infarction area in the Naomaitong group. In model rats, metabonomic analyses showed increased urinary levels of glutamate, taurine, trimetlylamine oxide, betaine, and glycine, and reduced levels of creatinine and creatine.Naomaitong regulated the metabolic changes by acting on multiple metabolic pathways, including glycine metabolism, glutaminolysis, transmethylation metabolism and creatinine metabolism.CONCLUSION: These data demonstrate that extract from Naomaitong is neuroprotective against focal cerebral ischemia induced by MCAO, and can alleviate biochemical changes in urinary metabolism. Metabonomics may be a useful approach for assessing the biochemical mechanisms underlying the neuroprotective actions of extract from Naomaitong.展开更多
目的研究脑脉通对大鼠脑缺血/再灌注(I/R)明胶酶系调节作用的影响。方法采用线栓法复制局灶性脑I/R模型,将大鼠分为假手术组、模型组、脑脉通组、尼莫地平组,后3组又分为脑缺血3h和I/R6、12、24h,3、6d亚组。采用免疫组化和酶谱分析等方...目的研究脑脉通对大鼠脑缺血/再灌注(I/R)明胶酶系调节作用的影响。方法采用线栓法复制局灶性脑I/R模型,将大鼠分为假手术组、模型组、脑脉通组、尼莫地平组,后3组又分为脑缺血3h和I/R6、12、24h,3、6d亚组。采用免疫组化和酶谱分析等方法,观察各组微血管结构、明胶酶及其抑制物的变化。结果脑脉通可降低模型组(I/R 24h～6d)MMP-2、MMP-9(I/R 12h～3d)的蛋白表达,提高模型组(I/ R 12h～6d),TIMP-1的蛋白表达。另外,各组MMP-2与MMP-9的酶谱分析比较,其量的变化与免疫表达规律基本一致。结论脑脉通对大鼠脑I/R微血管基底膜损伤的保护作用与其对明胶酶系调节有关。展开更多
基金Supported by National Natural Science Foundation of China(Study on the Material Basis and the Ratio of the Effective Components of Naodesheng Based on the Combination of Fingerprint and Metabolic Network,No.81274059Study on the Material Basis of Naomaitong in the Treatment of Ischemic Stroke Based on the in vivo Dynamic Effect and Bioinformatics,No.81274060Study on the in vivo Process and Compatibility Rule of Naomaitong Based on the PK-PD of Effective Components and the Multiobjective Optimization,No.81473413)
文摘OBJECTIVE: To examine the neuroprotective effect of extract from Naomaitong following focal cerebral ischemia reperfusion induced by occlusion of middle cerebral artery(MCA), and to determine the biochemical alterations in urine using proton nuclear magnetic resonance spectroscopy and principal component analysis.METHODS: Wistar rats were randomly assigned tothree groups: sham-operated group, MCA focal cerebral ischemia reperfusion model group, and active extract of Naomaitong treatment group. The model was established by an improved MCA occlusion(MCAO) method. Sham-operated rats received the same surgical procedure, but without occlusion. The Naomaitong treatment group were treated with active extract from Naomaitong at a dose of3.0 g·kg-·1d-1. Brain tissues and urine samples were collected from all groups for histopathological assessment and proton nuclear magnetic resonance spectroscopy-based metabonomics, respectively.RESULTS: Hematoxylin-eosin and triphenyl tetrazolium chloride staining of brain tissues showed a significant decrease in cerebral infarction area in the Naomaitong group. In model rats, metabonomic analyses showed increased urinary levels of glutamate, taurine, trimetlylamine oxide, betaine, and glycine, and reduced levels of creatinine and creatine.Naomaitong regulated the metabolic changes by acting on multiple metabolic pathways, including glycine metabolism, glutaminolysis, transmethylation metabolism and creatinine metabolism.CONCLUSION: These data demonstrate that extract from Naomaitong is neuroprotective against focal cerebral ischemia induced by MCAO, and can alleviate biochemical changes in urinary metabolism. Metabonomics may be a useful approach for assessing the biochemical mechanisms underlying the neuroprotective actions of extract from Naomaitong.
文摘目的研究脑脉通对大鼠脑缺血/再灌注(I/R)明胶酶系调节作用的影响。方法采用线栓法复制局灶性脑I/R模型,将大鼠分为假手术组、模型组、脑脉通组、尼莫地平组,后3组又分为脑缺血3h和I/R6、12、24h,3、6d亚组。采用免疫组化和酶谱分析等方法,观察各组微血管结构、明胶酶及其抑制物的变化。结果脑脉通可降低模型组(I/R 24h～6d)MMP-2、MMP-9(I/R 12h～3d)的蛋白表达,提高模型组(I/ R 12h～6d),TIMP-1的蛋白表达。另外,各组MMP-2与MMP-9的酶谱分析比较,其量的变化与免疫表达规律基本一致。结论脑脉通对大鼠脑I/R微血管基底膜损伤的保护作用与其对明胶酶系调节有关。
