基于NMR代谢组学研究脑脉通复方提取物对大鼠脑缺血再灌注模型的影响

Study on effects of extract in Naomaitong Formula on cerebral ischemia-reperfusion model based on NMR metabolomics

目的从整体上阐明脑脉通复方提取物不同剂量对脑缺血再灌注大鼠模型的作用及相关机制,以优选最佳剂量。方法采用改进的大脑中动脉阻断法(MCAO)建立Wistar大鼠局灶性脑缺血再灌注模型,应用核磁共振技术(NMR)和主成分分析(PCA)方法分析给予大鼠脑脉通复方提取物(1.5、3.0、6.0 g/kg)后,大鼠血浆代谢物变化,并结合脑组织病理切片HE染色检测,明确脑脉通复方提取物对脑缺血再灌注模型大鼠的治疗作用。结果 PCA分析和SPSS统计结果显示,脑脉通复方提取物中剂量(3.0 g/kg)能够很好地抑制MCAO引起的大鼠血浆中谷氨酰胺、牛磺酸、酪氨酸、乳酸升高;提高脂类、胆固醇、3-羟基丁酸、N-乙酰天门冬氨酸、乙酰乙酸、谷氨酸、胆碱的水平,使之趋向于正常。结论脑脉通复方提取物中剂量能够很好地调节大鼠脑缺血再灌注后的代谢平衡,从而起到抗脑缺血再灌注损伤的作用。

Objective To clarify the effects of the extract in Naomaitong Formula（ENF） at different doses on cerebral ischemia-reperfusion model of rats and its mechanism in order to optimize the dose group.Methods The focal cerebral ischemia-reperfusion model of Wistar rats was established by an improved middle cerebral artery occlusion（MCAO） method.NMR and principal component analysis（PCA） were applied to analyzing the changes of rat plasma metabolites by ig administration of ENF at 1.5,3.0,and 6.0 g/kg.And the treatment of ENF for cerebral ischemia-reperfusion model of rats was testified by HE staining with rat brain tissue biopsy.Results PCA and SPSS analyses indicated that the ENF at middle dose of 3.0 g/kg could inhibit the increase of glutamine,taurine,tyrosine,and lactic acid in the plasma of rats,promote the level of lipid,cholesterol,trihydroxy-butyric acid,N-acetyl aspartic acid,acetacetic acid,glutamic acid,and choline,and make them tend to normal.Conclusion Middle dose of ENF could efficiently regulate the metabolic balance after cerebral ischemia-reperfusion injury of rats,so as to play a role of resisting the cerebral ischemia-reperfusion injury of rats.