丹参酮提取物与相应主要单体在前列腺屏障转运的比较研究

Comparison on blood-prostate barrier permeability of tanshinone extract and corresponding major monomers

该研究考察了丹参酮提取物(tanshinone extract,Tan E)中主要单体成分丹参酮ⅡA(tanshinoneⅡA,TanⅡA)和隐丹参酮(cryptotanshinone,CTS)透过前列腺屏障以及在前列腺组织中的分布情况,并与等剂量相应单体成分分别给药后的情况进行了比较。采用人前列腺上皮细胞RWPE-1细胞体外培养21 d,建立前列腺屏障转运模型,考察TanⅡA和CTS在屏障模型上的透过率。SD大鼠灌胃给予Tan E(700 mg·kg^(-1))、CTS(29 mg·kg^(-1))、TanⅡA(50 mg·kg^(-1))后于2、4、8、12、24 h采集血浆及前列腺组织样品,测定生物样本中的TanⅡA和CTS的浓度。在细胞单层转运模型上,提取物组各时间点的CTS、TanⅡA累积转运量均高于相对应的单体给药组(P<0.01)。在动物水平上,Tan E给药后大鼠血浆以及前列腺组织中的TanⅡA及CTS浓度高于相应单体给药组。该研究显示Tan E中的共存成分对其主要药理活性单体成分TanⅡA及CTS透过前列腺屏障有促进作用,为丹参用于临床治疗前列腺相关疾病提供理论基础和实验依据。

In this study,the transmittance of tanshinoneⅡ_(A)(TanⅡ_(A))and cryptotanshinone(CTS)through the blood-prostate barrier and their distributions in the prostate tissue were compared between tanshinone extract(Tan E)treatment group and the corresponding monomer composition group under the equivalent dose conversion in vitro and in vivo.First,the human prostate epithelial cell line RWPE-1 was cultured in vitro for 21 days for the establishment of a blood-prostate barrier model,and the transmission of TanⅡ_(A)and CTS through the barrier model was investigated after administration of Tan E and corresponding single active components.Second,SD rats were administrated with 700 mg·kg^(-1)Tan E,29 mg·kg^(-1)CTS,and 50 mg·kg^(-1)TanⅡ_(A)by gavage,and plasma and prostate tissue samples were collected at the time points of 2,4,8,12,and 24 h.The TanⅡ_(A)and CTS concentrations in the samples were determined.The results showed that in the cell model,the cumulative transmission amounts of CTS and TanⅡ_(A)in the extract at each time point were higher than those of the corresponding single active components(P<0.01).In rats,after the administration of Tan E,the concentrations of TanⅡ_(A)and CTS in rat plasma and prostate were higher than those of the corresponding single active components.This study demonstrated that the coexisting components in Tan E promoted the penetration of its main pharmacological components TanⅡ_(A)and CTS through the blood-prostate barrier.The findings provide a theoretical and experimental basis for the application of Tan E in the clinical treatment of prostate-related diseases.