Objective The purpose of this study is to elucidate the neuroprotective effects of capsaicin pretreatment on ischemic stroke rats revealed by GC-MS metabolomicapproach .Methods The establishment of middle cerebral artery occlusion is a ideal method to mimic cerebral ischemia reperfusion injury .Twenty-four adult SD rats were randomly divided into three groups:sham group (Sham),model group (Mod) and capsaicin pretreatment group (CAP,0.2 mg/Kg).The cerebral cortex tissues were collected using GC-MS metabolomic approach and the screening of differential expressed metab-olites were adopted by multivariate statistical analyses including PCA analysis , partial least squares discriminant analysis ( PLS-DA) and orthogonal partial least squares discriminant analysis ( OPLS-DA) .Results OPLS-DA score plot can ob-viously distinguish each group and the screening methods of differentially expressed metabolites were according to the VIP value and the loading scatter plot combined with t-test (P<0.05).The analytical results showed that the metabolism spec-trum in model group was different from sham group ,excitatory amino acid glutamic acid (P<0.05) metabolites were signif-icantly increased while arachidonic acid (P<0.01)and some amino acid such as isoleucine (P<0.001),methionine(P<0.001),L-cysteine(P<0.001),aspartic acid(P<0.05),phenylalanine(P<0.05) and energy metabolites such as 1-phosphate-glucose(P<0.05)、6-phosphate-glucose(P<0.01)significantly decreased.Compared with model group,the metabolism spectrum of capsaicin pretreatment group represents a distinct metabolism spectrum ,inosine,isoleucine,methio-nine,L-cysteine,aspartic acid,phenylalanine and other amino acids were approaching to normal levels ,3,5-dihydroxy phen-yl glycine (P<0.001) and other metabolites significantly increased .Conclusion These differentially expressed metabo-lites are related to the disturbance in energy metabolism ,glycometabolism .Capsaicin pretreatment may improve energy me-tabolism,alleviate the release of excitatory glutamate ,improve the biological function of membrane to provide the neuropro-tective effects.In summery,GC-MS metabolomic approach can comprehensively reflect the general metabolic changes under the drug intervention and explore the underlying mechanism , which is helpful to further understanding the therapeutical mechanism of cerebral ischemia reperfusion injury .
本文利用in viuo治疗模型对关于5-Fu和IFN-a抗肿瘤协同作用机理进行了研究。人肝细胞癌细胞株PLC/PLE/5,接种到裸鼠背部皮下,复制裸鼠模型,分为对照组、5-Fu治疗组、IFN-a治疗组以及5-Fu/IFN-a联合用药组并检测5-Fu体内代谢相关酶的活性。5-Fu以0.5mg/只,腹腔注射,IFN-a以10万IU/只,皮下注射,3次/w。用药后1h、48h、7d分别取各组裸鼠肿瘤组织进行5-Fu体内代谢相关酶—thymidylate synthase(TS),dihydropyrimidine dehydrogenase(DPD),thymidinphos phorylase(TP)、orotate phosphoribosyl transferase(OPRT)、uridine phosphorylase(UP)等酶的活性测定。结果5-Fu治疗组、IFN-a治疗组以及联合用药组之间的5-Fu代谢相关酶活性未发现显著性差异,由此推测肝细胞癌治疗中5-Fu+IFN-a联合治疗中,IFN-a对5-Fu代谢相关酶的生物调节作用并不显著。