Li Jing-Xian, Yang Xiao-Qian, Tang Biao, Liu Xiao-Dan, Tang Ying-Hong, Deng Chang-Qing, Huang Xiao-Ping
Key Laboratory of Hunan Province for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, China.
Zhongguo Zhong Yao Za Zhi. 2017 Oct;42(19):3786-3794. doi: 10.19540/j.cnki.cjcmm.20170901.013.
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.
目的是研究黄芪甲苷（AST Ⅳ）联合三七总皂苷（PNS）对脑缺血再灌注损伤的影响，并通过脑缺血再灌注大鼠体内AST Ⅳ、人参皂苷Rg₁（Rg₁）、人参皂苷Rb₁（Rb₁）、三七皂苷R₁（R₁）这四种主要成分的药代动力学来探讨其协同作用机制。采用改良线栓法建立大鼠脑缺血/再灌注模型后，运用神经功能评分、脑梗死面积及病理形态学来评价AST Ⅳ与PNS联合拮抗脑缺血再灌注损伤的药理作用；采用超高效液相色谱串联质谱法（UPLC-MS/MS）测定不同时间点大鼠血浆中AST Ⅳ、Rg₁、Rb₁、R₁的含量，计算药代动力学参数并分析主要有效成分的药代动力学变化。结果显示，AST Ⅳ、PNS单独及二者联合均可减小大鼠脑梗死面积，减轻神经功能缺损行为评分，改善脑缺血后的病理变化，联合用药效果更佳。在AST Ⅳ、Rg₁、Rb₁、R₁中，曲线下面积（AUC）显著增大，平均驻留时间（MRT0-t）延长，峰浓度（Cmax）显著升高，表观分布容积（Vz/F）减小，体内清除率显著减慢。提示AST Ⅳ联合PNS对脑缺血/再灌注损伤具有协同增强作用，且使主要有效成分的药代动力学行为发生改变，其机制可能与延长有效成分在脑缺血状态下的滞留时间、提高生物利用度有关。
