基于1H-NMR的人参总皂苷治疗缺血性脑中风的血清代谢组学研究

Effect of ginsenosides on serous metabonomic profiles in cerebral ischemia-reperfusion rats based on 1H-NMR

课题组基于1H-NMR研究人参总皂苷对大脑中动脉闭塞(MCAO)模型大鼠血清代谢组的影响。实验将48只Wistar雄性大鼠随机分为6组:假手术组、模型组、阳性药组(6 mg·kg-1·d-1)和人参总皂苷高、中、低剂量组(200,100,50 mg·kg-1·d-1)。实验采用预给药,造模前连续给药5 d,末次给药后2 h,开始造模,采用改良的Longa线栓法制备大脑中动脉闭塞(MCAO)模型,假手术组只暴露左侧血管不做插线处理,所有大鼠只栓塞左侧大脑中动脉。2 h后轻轻撤出线栓,术后观察大鼠的外观,反应和活动情况,并进行神经症状评分。术后24 h各组眼后静脉丛采血,一定方法处理后采集1H-NMR谱,并用主成分分析方法对其进行分析。与假手术组比较,模型组的乳酸、谷氨酸、牛磺酸、胆碱、葡萄糖、蛋氨酸的含量显著升高(P<0.05),3-羟基丁酸、脂质和磷酸肌酸/肌酸的含量显著性降低(P<0.05)。与模型组比较,人参皂苷组的脂质、3-羟基丁酸酯、磷酸肌酸/肌酸含量显著增加(P<0.05),柠檬酸、胆碱、牛磺酸、葡萄糖和蛋氨酸的含量有变化,但没有显著性差异,乳酸和谷氨酸显著性降低(P<0.01)。结果表明人参总皂苷对大鼠脑缺血再灌注有保护作用,也可以调节代谢紊乱,促进新陈代谢回归表型到正常范围。

Serum metabonomic profiles of the model of focal cerebral ischemia reperfusion is established with the suture-occluded method by Longa to study the effect of ginsenosides.In this study,48 rats were randomly divided into six groups:sham-operated group,pathological model group,positive drug group(6 mg·kg-1·d-1)and high,medium,low-dose ginsenosides groups(200,100,50 mg·kg-1·d-1).They are given intragastric administration respectively with same amount of 0.5%CMC-Na,nimodipine and ginsenoside for 5 days.At 2 h after the final administration,the model was established with the suture-occluded method,and free radical-scavenging activity changes of ginsenoside were observed by maillard reaction,and Longa was possible used as a renoprotective agent-occluded method.At the end of 24 h after the reperfusion,the hemolymph of rats in each group was collected,and the 1H-NMR spectrum was collected after being treated by certain methods,and analyzed by principal component analysis(PCA).Compared with sham-operated group,pathological model group showed significant increases in the levels of lactate,glutamate,taurine,choline,glucose and methionine,but decreases in the levels of 3-hydroxybutyrate and phosphocreatine/creatine in serum.After treatment with ginsenosides,lipid,3-hydroxybutyrate and phosphocreatine/creatine were increased in the serum of ginsenosides group rats,but with decreases in lactate and glutamate.The results showed that ginsenosides could regulate metabolic disorders in rats with focal cerebral ischemia reperfusion,and promote a recovery in the process of metabolism.It′s helpful to promote the metabolic changes in rats with focal cerebral ischemia reperfusion via 1H-NMR,and lay a foundation to develop ginsenosides as a new drug to treat ischemic cerebral paralysis.