| Objectives（1）To study the changes of endogenous metabolites of urine after myocardial ischemia-reperfusion injury（MIRI）rats that were treated with Mongolian prescription Roudoukou-8 San.And to explore the pathogenesis of MIRI and the preventive mechanism of the prescription;（2）To compare the preventive effects and mechanism of different animal heart compatibility with Roudoukou-8 San on MIRI rats.Methods UPLC-Q-Exactive-MS technique was used to characterize the metabolites in the urine of control group,model group,positive control group and different animal heart-matched Roudoukou-8 San groups.Principal component analysis（PCA）and orthogonal partial least squares discriminant analysis（OPLS-DA）were performed using SIMCA 14.1 software to screen potential biomarkers.The chromatographic conditions were as follows:the column of Hypersil GOLD C18（2.1mm×100 mm,1.9μm）was used with the mobile phase of acetonitrile-0.1%aqueous formic acid using gradient elution at a flow rate of 0.2 mL·min-1.And the column temperature was 40°C with the sample volume that was 1μL.The Mass spectrometry conditions were as follows:electrospray ion source injection voltage was 4 kV and capillary temperature was 350°C.Ion transfer tube temperature was100°C and sheath gas flow rate was 5.2 L·min-1.What’s more,auxiliary gas flow rate was 0.6 L·min-1.The mass spectrometer resolution was 70000.Acquisition time was17 minutes.The scanning range was m/z 50750,and the positive ion scanning mode was adopted.Results（1）The quality of the OPLS-DA model established for the control group,model group,Roudoukou-8 San group and positive control group was better than that of the PCA model.The score map showed that Roudoukou-8 San group intersects control group away from model group;positive control group was far away from model group and had a tendency to recover from control group.Roudoukou-8 San reversed the content of 7 potential biomarkers in MIRI.The contents of proline,pantothenic acid,isoleucine and hippuric acid were significantly up-regulated,and the contents of creatine,creatinine and L-carnitine were significantly down-regulated.These seven biomarkers are mainly associated with the"biosynthesis of valine,leucine and isoleucine"and the"meta-acid and coenzyme A biosynthesis"metabolic pathways.（2）The quality of the OPLS-DA model established by control group,model group and different animal heart compatibility Roudoukou-8San groups was better than the PCA model.The score map showed that the different animal heart compatibility prescriptions had different prevention effects on MIRI.The four groups all showed a tendency to recover from control group away from model group.However,the yak heart compatibility Roudoukou-8 San group had a small part that coincides with control group.The ox heart and the pig heart compatibling with the Roudoukou-8 San group respectively were closed to the control group,and the rabbit heart is similar to Roudoukou-8 San group.Yak heart compatibility Roudoukou-8 San can regulate 7 of these metabolites.Ox heart compatibility Roudoukou-8 San can regulate 6 of these metabolites.Pig heart compatibility Roudoukou-8 San can regulate 6 of these metabolites.Rabbit heart compatibility Roudoukou-8 San can only regulate 2 of these metabolites.Conclusions（1）Mongolian medicine prescription Roudoukou-8 San can effectively regulate the imbalance of sugar,fat,amino acid and energy metabolism associated with metabolism in MIRI model rats and prevent MIRI rats through multi-channel,multi-channel and multi-target.（2）Roudoukou-8 San,which is compatible with different animal hearts,has a preventive effect on MIRI rats.Among them,Roudoukou-8 San,which is compatible with yak heart,has many types of metabolites regulated,and the mechanism involved is more complicated.It has the strongest preventive effect on MIRI.Roudoukou-8 San which is compatible with the oxen and Roudoukou-8 San which is compatible with the pig heart are followed.The rabbit heart-compatible Roudoukou-8 San is able to regulate the improved metabolites with limited and the worst results. |
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