摘要
目的采用代谢组学检测技术评价血府逐瘀汤对缺血性脑卒中(CIS)大鼠的保护作用并探究其代谢通路机制。方法SD大鼠(8周龄,雄性) 30只随机分为假手术组、模型组(缺血性脑卒中模型)和中药治疗组,每组10只。采用线栓法建立缺血性脑卒中大鼠模型。中药治疗组于造模前后给予血府逐瘀汤液[含生药10 g/(kg·d)]连续灌胃2周治疗,假手术组和模型组给予等量生理盐水,并进行神经行为学评分。灌药2周后采用超高效液相-四极杆飞行时间串联质谱仪(UPLCQTOF-MS/MS)法检测各组大鼠血清代谢谱的变化情况,用主成分分析(PCA)和正交偏最小二乘法判别分析(OPLS-DA)对检测结果作多元变量统计分析,筛选差异代谢物,并作代谢通路分析。结果模型组与假手术组对比,筛选出16个差异代谢物,其中显著上调的代谢物12个,下调的4个;中药治疗组与模型组相比,筛选出14个差异代谢物,其中显著上调的有4个代谢物,显著下调的有10个代谢物。在模型组上调的12个代谢物中,其中有7个代谢物在中药治疗组下调;在模型组下调的4个代谢物中,其中有3个在中药治疗组中下调。血府逐瘀汤对CIS保护作用的代谢途径主要有氨基酸代谢(丙氨酸、天冬氨酸和谷氨酸代谢,精氨酸和脯氨酸代谢,甘氨酸、丝氨酸和色氨酸代谢)、鞘磷脂代谢和丁酸代谢等。结论血府逐瘀汤液对缺血性脑卒中大鼠的治疗作用与氨基酸代谢和脂代谢有关。
Objective To explore the protective effect of Xuefu Zhuyu decoction against cerebral ischemic stroke(CIS)in rats and its metabolic mechanism by metabolomics study.Methods Thirty SD rats(8weeks old,male)were randomly divided into sham operation group,model group(ischemic stroke model)and treatment group,with 10 rats in each group.A rat model of ischemic stroke was established by suture method.The rats in treatment group were continuously gavaged with the Xuefu Zhuyu decoction[containing crude drug10g/(kg·d)]for 2 weeks,while the rats in sham operation group and model group were given the same amount of normal saline.The neurobehavioral score was recorded.After five weeks,UPLC-QTOF-MS/MS was used to detect the changes of serum metabolic profiles in each group,principal component analysis(PCA)and orthogonal partial least squares discrimination analysis(OPLSDA)were performed to analyze the multivariate variables for screening the differential metabolites and analyzing the metabolic pathway.Results Sixteen different metabolites were screened in model group compared with sham operation group,of which12were significantly up-regulated and4were down-regulated.Compared with model group,14differential metabolites were screened,of which4metabolites were significantly up-regulated and 10 metabolites were significantly down-regulated.Among the 12 up-regulated metabolites in model group,7 were down-regulated in treatment group.Of the4down-regulated metabolites in model group,3were down-regulated in treatment group.The metabolic pathways of Xuefu Zhuyu decoction against CIS mainly included amino acid metabolism(alanine,aspartic acid and glutamate metabolism,arginine and proline metabolism,glycine,serine and tryptophan metabolism),sphingomyelin metabolism and butyric acid metabolism.Conclusion The protective effect of Xuefu Zhuyu decoction against ischemic stroke rats is related to amino acid metabolism and lipid metabolism.
作者
徐敉
许春立
XU Mi;XU Chunli(Department of Internal Medicine,Shanghai Hudong Hospital,Shanghai 200129;Department of Neurology,Seventh People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine)
出处
《山西医科大学学报》
CAS
2018年第12期1442-1446,共5页
Journal of Shanxi Medical University
