基于药代动力学的山豆根抗炎作用机制研究

Study on anti-inflammation mechanism of Radix et Rhizome SophoraeTonkinensisin rat based on profile of pharmacokinetic parameters

目的基于药代动力学研究山豆根对角叉菜胶致大鼠足跖肿胀模型的抗炎作用及机制。方法雄性SD大鼠分为空白对照组、氢化可的松组(40 mg·kg^-1)、山豆根水提浸膏粉高剂量组(生药0.6 g·kg^-1)和低剂量组(生药0.3 g·kg^-1),测定致炎前和致炎后0.5、1、2、和3 h足跖肿胀度、致炎组织中炎症因子TNF-α、IL^-1β和IL-6含量及血中苦参碱、氧化苦参碱药代动力学参数。结果氢化可的松组致炎后肿胀率明显降低(P<0.01),山豆根水提浸膏粉组致炎后肿胀率亦降低(P<0.05)且体内苦参碱含量呈剂量依赖性,高剂量组AUC值约为低剂量组两倍,达峰时间与抗炎作用高峰时间一致;山豆根水提浸膏粉可显著下调炎症因子含量(P<0.01),抑制其表达的作用呈剂量依赖性。结论山豆根对角叉菜胶致大鼠足跖肿胀模型具有抗炎作用,且呈剂量依赖性,与体内苦参碱系统暴露量成正相关,抗炎机制与抑制炎症因子表达有关。

Aim To study the anti-inflammation effect of Radix et Rhizome Sophorae Tonkinensis(short for“RRST”)in rat paw edema induced by carrageenan based on pharmacokinetic parameters and its mechanism.Methods Male SD rats were divided into four groups:control group,hydrocortisone group(40 mg·kg^-1),water extract powder of RRST high-dose group(0.6 g·kg^-1)and low-dose group(0.3 g·kg^-1)(short for“RRST-H”and“RRST-L”).The rat paw volume was measured before and 0.5,1,2 and 3 h after model establishment,and the contents of TNF-α,IL^-1βand IL-6 in the inflammatory tissues were tested after the last measurement of paw volume,and plasma was collected from the posterior orbital venous plexus to explore the profile pharmacokinetic parameters of matrine and oxymatrine.Results Compared with control group,the swelling rate significantly decreased in hydrocortisone group after model establishment(P<0.01),and the swelling rate significantly decreased as the same points as hydrocortisone group in RRST-treated group(P<0.05).There was dose-dependent relationship of RRST total exposure in plasma,which proportionally increased with the dose increasing.The AUC value of matrine was about twice that of the low-dose group,which was consistent with the strongest anti-inflammation point.The content of inflammatory factors in the inflammatory tissues were markedly down-regulated in RRST-treated groups in a dose-dependent manner(P<0.01).Conclusions RRST shows anti-inflammation effect in a dose-dependent manner,which is positively related to the total exposure of matrine in plasma,and the anti-inflammatory mechanism is related to the inhibition of the expression of inflammatory factors.