黄芪甲苷和三七总皂苷配伍抗大鼠脑缺血再灌注损伤及其药动学的研究(1)
[摘要] 研究黄芪甲苷(AST Ⅳ)和三七总皂苷(PNS)配伍对大鼠脑缺血再灌注损伤的影响，并从4种主要有效成分AST Ⅳ、人参皂苷Rg1(Rg1)、人参皂苷Rb1(Rb1)、三七皂苷R1(R1)在脑缺血再灌注大鼠体内的药动学行为探讨二者协同增强抗脑缺血再灌注损伤的机制。采用改良线栓法制备大鼠大脑中动脉栓塞脑缺血/再灌注模型，以神经功能评分、脑梗死面积、病理形态学指标综合评价AST Ⅳ和PNS配伍抗脑缺血再灌注损伤的药理效应；采用高效液相色谱-串联四极杆质谱法(UPLC-MS/MS)測定给药后不同时间大鼠血浆中AST Ⅳ，Rg1，Rb1，R1的含量，计算药代动力学参数，分析AST Ⅳ和PNS配伍后主要有效成分药代动力学行为的变化。结果发现AST Ⅳ，PNS单用及其配伍可以缩小大鼠脑梗死面积，降低神经功能缺失行为学评分，改善脑缺血后病理形态变化，AST Ⅳ和PNS配伍的效应强于二者单用。药代动力学分析结果，AST Ⅳ和PNS配伍后，AST Ⅳ，Rg1，Rb1，R1的曲线下面积(AUC)显著增加，平均驻留时间MRT0-t延长，达峰浓度(Cmax)显著增加，表观分布容积(Vz/F)减少，且体内清除速率显著减慢。表明AST Ⅳ和PNS配伍具有协同增强抗脑缺血再灌注损伤的作用，且二者配伍可使主要有效成分的药动学行为发生改变，提示其机制可能是AST Ⅳ和PNS配伍后，可在脑缺血状态下延长药物的体内滞留时间，使生物利用度增加，达到增强药效、延长药效、发挥协同增效的目的。
, http://www.100md.com
[关键词] 黄芪甲苷； 三七总皂苷； 配伍； 脑缺血再灌注； 药动学
[Abstract] The aim is to study the effect of astragaloside Ⅳ (AST Ⅳ) combined with Panax notoginseng saponins (PNS) on cerebral ischemia-reperfusion injury， and to probe the synergistic mechanism through the pharmacokinetics of the four major components such as AST Ⅳ， ginsenoside Rg1 (Rg1)， ginsenoside Rb1 (Rb1)， notoginsenoside R1 (R1) in cerebral ischemia-reperfusion rats. Following the establishment of cerebral ischemia/reperfusion model in rats by modified suture method， neurological function score， cerebral infarction area and pathomorphology were used to evaluate the pharmacological effect that the combination of AST Ⅳ and PNS antagonized cerebral ischemia-reperfusion injury； the contents of AST Ⅳ， Rg1， Rb1， R1 in rat plasma of different time points were determined with ultra performance liquid chromatography tandem massspectrometry (UPLC-MS/MS)， pharmacokinetic parameters were calculated and pharmacokinetics changes of the main effective components were analyzed. The results showed that AST Ⅳ， PNS alone and their combination could reduce the cerebral infarction area of rats， relieve the behavioral scores of neurologic deficit， improve the pathological changes after cerebral ischemia， the effects of the combination were better. Among AST Ⅳ， Rg1， Rb1， R1， the area under the curve (AUC) was significantly increased， the mean residence time of (MRT0-t) was delayed， the peak concentration (Cmax) was significantly raised， the apparent volume of distribution (Vz/F) was reduced， and the clearance rate in vivo was significantly slowed. It suggested that AST Ⅳ combined with PNS has synergistic enhancement on anti-cerebral ischemia/reperfusion injury， moreover， make the pharmacokinetic behavior of the main effective components change， the mechanism may be associated with prolonging the retention time of the effective components in cerebral ischemia condition， elevating the bioavailability., 百拇医药(李静娴 杨筱倩 唐标 刘晓丹 唐映红 邓常清 黄小平)
, http://www.100md.com
[关键词] 黄芪甲苷； 三七总皂苷； 配伍； 脑缺血再灌注； 药动学
[Abstract] The aim is to study the effect of astragaloside Ⅳ (AST Ⅳ) combined with Panax notoginseng saponins (PNS) on cerebral ischemia-reperfusion injury， and to probe the synergistic mechanism through the pharmacokinetics of the four major components such as AST Ⅳ， ginsenoside Rg1 (Rg1)， ginsenoside Rb1 (Rb1)， notoginsenoside R1 (R1) in cerebral ischemia-reperfusion rats. Following the establishment of cerebral ischemia/reperfusion model in rats by modified suture method， neurological function score， cerebral infarction area and pathomorphology were used to evaluate the pharmacological effect that the combination of AST Ⅳ and PNS antagonized cerebral ischemia-reperfusion injury； the contents of AST Ⅳ， Rg1， Rb1， R1 in rat plasma of different time points were determined with ultra performance liquid chromatography tandem massspectrometry (UPLC-MS/MS)， pharmacokinetic parameters were calculated and pharmacokinetics changes of the main effective components were analyzed. The results showed that AST Ⅳ， PNS alone and their combination could reduce the cerebral infarction area of rats， relieve the behavioral scores of neurologic deficit， improve the pathological changes after cerebral ischemia， the effects of the combination were better. Among AST Ⅳ， Rg1， Rb1， R1， the area under the curve (AUC) was significantly increased， the mean residence time of (MRT0-t) was delayed， the peak concentration (Cmax) was significantly raised， the apparent volume of distribution (Vz/F) was reduced， and the clearance rate in vivo was significantly slowed. It suggested that AST Ⅳ combined with PNS has synergistic enhancement on anti-cerebral ischemia/reperfusion injury， moreover， make the pharmacokinetic behavior of the main effective components change， the mechanism may be associated with prolonging the retention time of the effective components in cerebral ischemia condition， elevating the bioavailability., 百拇医药(李静娴 杨筱倩 唐标 刘晓丹 唐映红 邓常清 黄小平)