[Plasma metabonomics study of ischemic cerebral apoplexy rats treated with Tongsaimai pellets].
OBJECTIVE
To observe abnormal metabolic changes caused by ischemic cerebral apoplexy and the regulating action of Tongsaimai pellets on abnormal metabolism by analyzing the change of small molecules in plasma of ischemic cerebral apoplexy rat. To find the potential biomarkers, and to explore metabolic mechanisms of Tongsaimai pellets.


METHODS
Rat models of middle cerebral artery occlusion was established with electric coagulation, and rats were divided into 4 groups, model group, sham-operation group, Tongsaimai pellets group and positive control group. Tongsaimai pellets and positive control group were orally administrated by 13.2 g x kg(-1) x d(-1) of crude drugs and 32 mg x kg(-1) x d(-1) of Nimodipine respectively, m odel and sham-operation group by equal volume of distilled water for a week. Plasma of model and sham-operation group were collected, and plasma of Tongsaimai pellets and positive control group were collected on the 1st, 3rd , 7th day after administration. Endogenous metabolites of four groups were determined with GC-MS. Partial least squares discriminant analysis (PLS-DA) was applied to analyze multivariate data and set up model, and T-test was used in significant statistical analysis.


RESULTS
Compared with sham-operation group rats, pyruvic acid, taurine and hydroxyproline obviously increased in model group rats, while lactic acid, glyceric acid, aminomalonic acid, fructose, tryptophan and leucine significantly decreased, so these metabolites were potential metabolic biomarkers. These endogenous metabolites except taurine got restoration in Tongsaimai group rats.


CONCLUSIONS
Abnormal metabolite level in plasma can be certainly recovered by Tongsaimai pellets, and the treatment of Tongsaimai pellets can be connected with the regulation of related metabolic pathways.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China.
Jiayu
J
Tu
Jiye
J
A
Guangji
G
Wang
Hongmei
H
Wen
Aiyun
A
Wang
Liuqing
L
Di
Bei
B
Cao
Linsheng
L
Liu
D000818:Animals; D002545:Brain Ischemia / Q000097:blood* / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005632:Fructose / Q000097:blood; D005988:Glyceric Acids / Q000097:blood; D006909:Hydroxyproline / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D007930:Leucine / Q000097:blood; D008297:Male; D008314:Malonates / Q000097:blood; D055432:Metabolomics / Q000379:methods*; D019289:Pyruvic Acid / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000097:blood* / Q000188:drug therapy*; D013654:Taurine / Q000097:blood; D014364:Tryptophan / Q000097:blood
D004365:Drugs, Chinese Herbal; D005988:Glyceric Acids; D008314:Malonates; C019249:aminomalonic acid; D013654:Taurine; D005632:Fructose; D019344:Lactic Acid; C042971:glyceric acid; D019289:Pyruvic Acid; D014364:Tryptophan; D007930:Leucine; D006909:Hydroxyproline