基于PK-PD模型评价脑脉通保护神经细胞的药效物质研究

Study on pharmacodynamic material basis of Naomaitong to protect neuronal cells based on PK-PD model

运用药效学和药动学的PK-PD相关性模型研究治疗脑卒中的临床经验方脑脉通抑制Na2S2O4和Glu诱导的PC12神经细胞死亡的物质基础。该实验分别建立Na2S2O4及Glu诱导的PC12细胞死亡模型,以LDH侧漏量、NO含量作为药效学指标,通过SVM算法建立PK-PD模型评价脑脉通抑制神经细胞死亡的有效成分。结果显示,在2种损伤模型中,大黄素甲醚-8-O-β-D-吡喃葡萄糖苷、芦荟大黄素、大黄酚、大黄酸、大黄素、人参皂苷Rg1、人参皂苷Rc、3’-甲氧基葛根素和藁本内酯的正相关性较大,明显改善了LDH释放量和NO含量。结果提示,脑脉通中葛根及大黄的贡献成分分别保护Na2S2O4及Glu因素诱导的神经细胞死亡,PK-PD模型为脑脉通筛选出的神经细胞保护成分,揭示了脑脉通治疗脑缺血损伤可能的药效物质基础。

The PK-PD correlation models by using pharmacodynamics and pharmacokinetics were applied to study the material basis of Naomaitong,a clinical empirical prescription for the treatment of cerebral apoplexy,in inhibiting the death of PC12 nerve cells induced by Na2S2O4 and Glu.In this experiment,PC12 cell death models induced by Na2S2O4 and Glu were established respectively.With LDH lateral leakage and NO content as pharmacodynamic indexes,PK-PD model was established by SVM algorithm to evaluate the effective components of Naomaitong in inhibiting neural cell death.The results showed that the positive correlation of emodin methyl ether-8-O-β-D-glucopyranoside,aloe emodin,chrysophanol,rhein,emodin,ginsenoside Rg1,ginsenoside Rc,3’-methoxypuerarin and ligustilide was significant,obviously improving the LDH release and NO content.The results indicated that the contribution of Radix Puerariae Lobatae Radix and Rhei Radix et Rhizoma in Naomaitong could protect the nerve cell death induced by Na2S2O4 and Glu respectively.PK-PD model was used to screen the neuroprotective components in Naomaitong,revealing the possible pharmacodynamic material basis of Naomaitong in the treatment of cerebral ischemia injury.