| Objective1. Study of different doses of puerarin by intraperitoneal injection in a dynamic process of blood and major organs and the brain tissue of normal rats Guinea organ distribution metabolism.2. Study different doses of puerarin by intraperitoneal injection dynamic changes in the blood and major organs and brain lesion cerebral ischemia-reperfusion injury model of rat hippocampal tissue around the distribution of metabolism.3. Comparison of different doses of puerarin by intraperitoneal injection in normal rats and cerebral ischemia-reperfusion injury in rats with metabolic tissue distribution of the similarities and differences, in order to provide pharmacokinetic data support for clinical useMethods1. The three different doses of puerarin distribution of pharmacokinetic study on behalf of the organization in normal rats:In accordance with the high dose group (80mg/ kg), middle dose group (40mg/kg), low dose group (20mg/kg) by intraperitoneal puerarin injection, after the first administration of anesthesia 5,15,30,60,90,120,180,240,300,360 minutes after abdominal aortic blood, blood perfusion through the heart, heart, liver, spleen, lung, kidney, hippocampus, cortex, striatum. After the samples were prepared by homogenization and centrifugation, the use of the content of indirect competitive ELISA test samples Puerarin law.2. The three different doses of puerarin distribution of pharmacokinetic study on behalf of the organization in cerebral ischemia-reperfusion injury model (MCAO) in rats: Preparation use thread method MCAO rat model of ischemia reperfusion 90min, while according to high dose group (80mg/kg), middle dose group (40mg/kg), low dose group (20mg/kg) by intraperitoneal injection puerarin, after administration 5,15,30,60,90,120 minutes after abdominal aortic blood, after taking blood by cardiac perfusion, heart, liver, spleen, lung, kidney, left hippocampus and right hippocampus. After the samples were prepared by homogenization and centrifugation, the use of the content of indirect competitive ELISA test samples Puerarin law.Results1.Different doses of puerarin in normal rat tissue distribution metabolic characteristics1.1 Pharmacokinetic characteristics in the bloodIn the high dose group, puerarin in the blood of rats have appeared two peaks. Low-dose group only one absorption peak.High, medium and low three different doses Cmax and AUC were significantly different (P<0.05). Tmax and MRT no significant difference (P>0.05).1.2 Pharmacokinetic characteristics in the heartThree different doses of puerarin were only there is a peak absorption in the heart tissue distribution of metabolic processes, the drug-metabolic curve trend is consistent.High, medium and low three different doses Cmax and AUC were significantly different (P<0.05), max and MRT no significant difference (P>0.05).1.3 Pharmacokinetic characteristics in the liverThree different doses of puerarin were only there is a peak absorption in the liver tissue distribution of metabolic processes, the drug-metabolic curve trend is consistent.High, medium and low three different doses Cmax and AUC were significantly different (P<0.05), Tmax and MRT no significant difference (P>0.05).1.4 Pharmacokinetic characteristics in the spleenThree different doses of puerarin were only there is a peak absorption in the spleen tissue distribution of metabolic processes, the drug-metabolic curve trend is consistent.High, medium and low three different doses Cmax and AUC were significantly different (P<0.05), MRT was no significant difference (P>0.05), high dose group had significant differences in, Tmax low dose group (P<0.05), Tmax high dose group than the low-dose group, middle dose group later extended by 15 minutes.1.5 Pharmacokinetic characteristics in the lungThree different doses of puerarin were only there is a peak absorption in the lung tissue distribution of metabolic processes, the drug-metabolic curve trend is consistent.High, medium and low three different doses Cmax and AUC were significantly different (P<0.05), Tmax and MRT no significant difference (P>0.05).1.6Pharmacokinetic characteristics in kidneyIn the high dose group and middle dose group, puerarin in both kidneys, there were two peaks. A low dose group only absorption peak in the first 15 minutes after administration.High, medium and low three different doses Cmax and AUC were significantly different (P<0.05), MRT was no significant difference (P>0.05). And in the high dose group, Tmax low-dose group were significantly different (P<0.05), the peak time of the high-dose group than in the low dose group dose group advance forward 10 minutes.1.7 Pharmacokinetic characteristics in the hippocampusThree different doses of puerarin were only there is a peak absorption in the hippocampal tissue distribution of metabolic processes, the drug-metabolic curve trend is consistent.High, medium and low three different doses Cmax and AUC were significantly different (P<0.05), Tmax and MRT no significant difference (P> 0.05).1.8 Different doses of puerarin pharmacokinetic characteristics in the cortexOrganization of three different doses of puerarin in cortical distribution of metabolic processes were only there is a peak absorption, drug-metabolic curve trend is consistent.High, medium and low three different doses Cmax and AUC were significantly different (P<0.05), Tmax and MRT no significant difference (P>0.05).1.9 Pharmacokinetic characteristics in the striatumThree different doses of puerarin in striatal tissue distribution of metabolic processes are only there is a peak absorption, drug-metabolic curve trend is consistent.High, medium and low three different doses Cmax and AUC were significantly different (P<0.05), Tmax and MRT no significant difference (P>0.05).2 Different doses of puerarin on MCAO rat model of tissue distribution pharmacokinetics.2.1 Pharmacokinetic characteristics in the bloodHigh, medium and low three different doses Cmax and AUC were significantly different (P<0.05).Tmax was no significant difference (P>0.05). High-dose group and middle dose group puerarin MRT no significant difference (P>0.05), and between the high-dose group and low dose group, middle dose group and low dose group were significantly different (P <0.05).2.2 Pharmacokinetic characteristics in the heartThree different doses of puerarin were only there is a peak absorption in the heart tissue distribution of metabolic processes, the drug-metabolic curve trend is consistent.High, medium and low three different doses Cmax and AUC were significantly different (P<0.05), Tmax and MRT no significant difference (P> 0.05).2.3 Different doses of puerarin pharmacokinetic characteristics in the liverThree different doses of puerarin were only there is a peak absorption in the liver tissue distribution of metabolic processes, the drug-metabolic curve trend is consistent.High, medium and low three different doses Cmax and AUC were significantly different (P<0.05), Tmax and MRT no significant difference (P> 0.05).2.4 Pharmacokinetic characteristics in the spleenThree different doses of puerarin were only there is a peak absorption in the spleen tissue distribution of metabolic processes, the drug-metabolic curve trend is consistent.High, medium and low three different doses Cmax and AUC were significantly different (P<0.05), Tmax and MRT no significant difference (P> 0.05).2.5 Pharmacokinetic characteristics in the lungsThree different doses of puerarin were only there is a peak absorption in the lung tissue distribution of metabolic processes, the drug-metabolic curve trend is consistent.High, medium and low three different doses Cmax and AUC were significantly different (P<0.05), Tmax and MRT no significant difference (P> 0.05).2.6 Pharmacokinetic characteristics in kidneyThree different doses of puerarin were only there is a peak absorption in the lung tissue distribution of metabolic processes, the drug-metabolic curve trend is consistent.High, medium and low three different doses Cmax and AUC were significantly different (P<0.05), Tmax and MRT no significant difference (P> 0.05).2.7 Pharmacokinetic characteristics in the left hippocampusThree different doses of puerarin were only there is a peak absorption in the hippocampal tissue distribution of metabolic processes, the drug-metabolic curve trend is consistent.High, medium and low three different doses Cmax and AUC were significantly different (P<0.05), Tmax and MRT no significant difference (P>0.05).2.8 Pharmacokinetic characteristics in the right hippocampusOrganization of three different doses of puerarin in cortical distribution of metabolic processes were only there is a peak absorption, drug-metabolic curve trend is consistent. High, medium and low three different doses Cmax and AUC were significantly different (P<0.05), Tmax and MRT no significant difference (P>0.05).Conclusions1.1 Puerarin on cerebral ischemia reperfusion injury in rat model of tissue distribution of metabolic processes in the blood and tissues and organs than normal peak time was prolonged.1.2Weight distribution of the high-dose group puerarin in model hippocampus was significantly higher than the normal group.1.3High and medium dose of puerarin in the hippocampus of model group of metabolic rate than normal rats quickly.1.4 Low doses of puerarin in model group hippocampus lesion residence time is longer than the undamaged parts of the hippocampus, a longer duration of action, metabolic more slowly. |
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