ABSTRACT
Aim To investigate the relationship between the brain targeting effect and P-glycoprotein(P-gp)expression level of Danshensu borneol ester(DBE)and the combination use of sodium Danshensu and borneol(SDSS-B).Methods The liquid chromatography mass spectrometry(LC-MS)method was applied to investigate the accumulation of Danshensu(DSS)in rat brain tissues after intravenous injection of DBE,SDSS-B and SDSS.Also their effect on regulating the expression level of P-gp in rat hippocampus was investigated using Western blot.Results The brain targeting effect of DBE,SDSS-B was qualitatively analyzed through the brain distribution of DSS,and the result was DBE(SDSS-B)>SDSS(P0.05 at 5,15,45,60 min,vs control group).Conclusion An attenuated expression level of P-gp can be realized by DBE and SDSS-B,which is advantageous to their brain targeting.
ABSTRACT
Aim To investigate the brain targeting of ginkgolide B prodrug (PGB ) and its mechanism. Methods The liquid chromatography tandem mass spectrometry (LC-MS /MS)method was applied to in-vestigate the pharmacokinetics of PGB in rat brain tis-sue after intravenous injection of PGB.Also the brain targeting was evaluated on the basis of the pharmacoki-netic parameter of PGB.The incomplete cerebral is-chemia model was induced in mouse,the effect of PGB on cerebral capillary permeability was observed by Ev-ans blue method.High performance liquid chromatog-raphy (HPLC)was used to determine the partition co-efficients (logP)of PGB in octanol-water system.PGB and P-glycoprotein (P-gp)was docked by using Mole-gro Virtual Docker (MVD)software to predict its bind-ing abilities with P-gp.The interaction of PGB with ATPase activity of human P-gp membrane was esti-mated by measuring inorganic phosphate liberation. Results The brain targeting of PGB was evaluated by treatment effective (TA ) and drug targeting index (DTI),the calculated value were 6.87 and 4.1 4 re-spectively.Preventive medication of PGB could signifi-cantly decrease cerebral capillary permeability (P <0.05).The lipo-hydropartition coefficient of PGB was higher than that of GB,their logP data were 1 .03 and 0.61 respectively.PGB displayed the stronger binding affinity with P-gp than GB according to the molecular docking calculations,their MolDock Score toward P-gp were -1 43.36 and -1 1 6.40KJ·mol -1 respectively. ATP-hydrolisis showed that PGB increased ATPase activity with a Km of approximately 237.75 μmol · L -1 ,however GB with a Km of approximately 841 .24μmol·L -1 .PGB might interact with P-gp with a high-er affinity and exhibit more effect than GB.Conclu-sion PGB is characterized by its brain targeting. Higher liposolubility of PGB results in good blood-brain permeability,which is advantageous to its brain targe-ting.Besides,PGB can effectively inhibit the efflux effect of P-gp to GB because of its increased P-gp AT-Pase activity.
ABSTRACT
The construction of a network resource data base for clinical skill teaching aiming at sharing excellent teaching resources was completed by integrating all kinds of teaching resource including characters,eourseware,pictures,cartoons,videos and examination questions,etc.In view of the generally weak situation of the current domestic education resource data base construction,the contents,guiding ideology,principle,object,orientation,function and the management mechanism of the network resource data base construction were devised for clinical skills teaching.Suggestions for specific ideas and construction problems were proposed to promote the construction and optimization of the network resource database for clinical skills teaching.