A preliminary study from our research group showed that picroside II inhibited neuronal apop- tosis in ischemic penumbra, reduced ischemic volume, and improved neurobehavioral function in rats with cerebral ischemia. ...A preliminary study from our research group showed that picroside II inhibited neuronal apop- tosis in ischemic penumbra, reduced ischemic volume, and improved neurobehavioral function in rats with cerebral ischemia. The aim of the present study was to validate the neuroprotective effects of picroside II and optimize its therapeutic time window and dose in a rat model of cerebral ischemia. We found that picroside Ⅱ inhibited cell apoptosis and reduced the expression of neuron-specific enolase, a marker of neuronal damage, in rats after cerebral ischemic injury. The optimal treatment time after ischemic injury and dose were determined, respectively, as follows: (1) 2.0 hours and 10 mg/kg according to the results of toluidine blue staining; (2) 1.5 hours and 10 mg/kg according to early apoptotic ratio by flow cytometry; (3) 2.0 hours and 10 mg/kg according to immunohistochemical and western blot analysis; and (4) 1.5 hours and 10 mg/kg according to reverse transcription polymerase chain reaction. The present findings suggest that an intraperitoneal injection of 10 mg/kg picroside II 1.5-2.0 hours after cerebral ischemic injury in rats is the optimal dose and time for therapeutic benefit.展开更多
The aim is to study the neuroprotective effect and optimize the therapeutic dose and time window of picrosede II by orthogonal test in cerebral ischemic injury in rats. The forebrain ischemia models of rats were estab...The aim is to study the neuroprotective effect and optimize the therapeutic dose and time window of picrosede II by orthogonal test in cerebral ischemic injury in rats. The forebrain ischemia models of rats were established by bilateral common carotid artery occlusion (BCCAO) methods. The successful models were randomly grouped according to orthogonal experimental design and treated by injecting picroside II intraperitonenally with different therapeutic dose at different ischemic time. The contents of aquaporins 4 (AQP4), matrix metalloproteinases 9 (MMP 9) and cyclooxygenase 2 (COX2) in brain tissue were determined by enzyme linked immunosorbent assay to evaluate the therapeutic effect of picroside II on cerebral ischemic injury. The results indicated that the best therapeutic time window and dose of picroside II in cerebral ischemic injury should be 1) ischemia 1.5 h with 20 mg/kg body weight according to the content of AQP4;2) ischemia 2.0 h with 20 mg/kg according to the content of MMP9;and 3) ischemia 1.5 h with 20 mg/kg according to the content of COX2 inbrain tissue. It is concluded that the optimized therapeutic dose and time window is injecting picroside II peritonenally with 10 - 20 mg/kg body weight at ischemia 1.5 - 2.0 h in cerebral ischemic injury according to the principle of lowest therapeutic dose with longest time window.展开更多
基金supported by the National Natural Science Foundation of China,No.81041092,81274116
文摘A preliminary study from our research group showed that picroside II inhibited neuronal apop- tosis in ischemic penumbra, reduced ischemic volume, and improved neurobehavioral function in rats with cerebral ischemia. The aim of the present study was to validate the neuroprotective effects of picroside II and optimize its therapeutic time window and dose in a rat model of cerebral ischemia. We found that picroside Ⅱ inhibited cell apoptosis and reduced the expression of neuron-specific enolase, a marker of neuronal damage, in rats after cerebral ischemic injury. The optimal treatment time after ischemic injury and dose were determined, respectively, as follows: (1) 2.0 hours and 10 mg/kg according to the results of toluidine blue staining; (2) 1.5 hours and 10 mg/kg according to early apoptotic ratio by flow cytometry; (3) 2.0 hours and 10 mg/kg according to immunohistochemical and western blot analysis; and (4) 1.5 hours and 10 mg/kg according to reverse transcription polymerase chain reaction. The present findings suggest that an intraperitoneal injection of 10 mg/kg picroside II 1.5-2.0 hours after cerebral ischemic injury in rats is the optimal dose and time for therapeutic benefit.
文摘The aim is to study the neuroprotective effect and optimize the therapeutic dose and time window of picrosede II by orthogonal test in cerebral ischemic injury in rats. The forebrain ischemia models of rats were established by bilateral common carotid artery occlusion (BCCAO) methods. The successful models were randomly grouped according to orthogonal experimental design and treated by injecting picroside II intraperitonenally with different therapeutic dose at different ischemic time. The contents of aquaporins 4 (AQP4), matrix metalloproteinases 9 (MMP 9) and cyclooxygenase 2 (COX2) in brain tissue were determined by enzyme linked immunosorbent assay to evaluate the therapeutic effect of picroside II on cerebral ischemic injury. The results indicated that the best therapeutic time window and dose of picroside II in cerebral ischemic injury should be 1) ischemia 1.5 h with 20 mg/kg body weight according to the content of AQP4;2) ischemia 2.0 h with 20 mg/kg according to the content of MMP9;and 3) ischemia 1.5 h with 20 mg/kg according to the content of COX2 inbrain tissue. It is concluded that the optimized therapeutic dose and time window is injecting picroside II peritonenally with 10 - 20 mg/kg body weight at ischemia 1.5 - 2.0 h in cerebral ischemic injury according to the principle of lowest therapeutic dose with longest time window.