To study the pharmacokinetic process of
Danshensu in cerebal
ischemia injury model rats and the correlation with its anti-
cerebral ischemia effect. In this study, the
middle cerebral artery occlusion (MCAO) model was established, in which all of the rats were intravenously injected of
Danshensu at a single dose of 40 mg x kg(-1). The HPLC-DAD method was applied to determine the plasma concentration of
Danshensu at different time points and draw the
drug-time curve. Meanwhile, the
superoxide dismutase (SOD) and the
lactate dehydrogenase (LDH) activity were determined to draw the time-effect curve. The
DAS 3.2. 6 software was used to process the data, analyze their correlation, compare the pharmacokinetic difference between model and normal rats after the administration of the same doses of
Danshensu and the changes in pharmacodynamic indicators of model rats after the administration, and evaluate the effect of
Danshensu in treating the
cerebral ischemia disease. According to the results, the pharmacokinetic processes of
Danshensu in the
cerebral ischemia-reperfusion and normal rats were consistent to the two-compartment model. The main pharmacokinetic parameters were: t1/2alpha were (0.267 +/- 0.026), (0.148 +/- 0.020) h;t1/2beta were (1.226 +/- 0.032), (1.182 +/- 0.082) h; AUC0-infinity were (42.168 +/- 4.007), (26.881 +/- 1.625) mg x L(-1) x h. After the
cerebral ischemia-reperfusion, the activity of SOD decreased and the activity of LDH increased.
Danshensu could inhibit the decrease in the SOD activity and the increase in the LDH activity within a certain period of time. This indicated that
Danshensu could stay longer in
cerebral ischemia-reperfusion rats than in normal rats and eliminated more slowly, which reflected the rationality of
Danshensu in the clinical treatment of
cerebral ischemia diseases.
Danshensu's effect against the cerebral ischemic injury may be related with its level in vivo. Its plasma concentration is positively related to the SOD activity and negatively related to the LDH activity.