Study On Regulation And Mechanism Of Borneol In Medicine "Uplink" Based On Opening BBB

Aim:Through the different time interval and different doses of borneol gardenoside of rat brain target effect;Through the micro dialysis-UPLC-MS bomeol platform for research on the influence of gardenoside pharmacokinetics in rats; Research by Western, RT-PCR bomeol ultrastructure of rats in different areas of ATP combination box. Discussed based on the property of a medicine borneol open blood-brain barrier "upward" mechanism.Methods:(1) a About 180 SD Rats, Divided into 4 groups randomly, for each group of 45 only. According to the time intervals between borneol and give gardenoside divided into 5 min and 15 min group of borneol and 30 min group, Another group is blank group. The group was given borneol lavage of borneol (0.2g·kg-1), Three group of borneol in lavage borneol, 5\15\30min after giving gardenoside (300mg·kg-1,iv). The Blank group only give gardenoside. Groups of animals give gardenoside after 0.5,1,5,10,15,30,45,60,90 min take blood、brain and weigh it. Plasma and brain specimens except protein, centrifugal, nitrogen dry and constant volume flow, take 10μL ready to sample. (1)b About 225 SD Rats, Divided into 4 groups randomly, for each group of 45 only. According to divided into borneol dose of 0.05 g/kg,0.1 g/kg,0.1 g/kg,0.4 g/kg group, Another group is blank group. Four synthetic borneol groups respectively to different dose of borneol, And give gardenoside after 15 min (300mg·kg-1,iv).Only injection gardenoside in blank group. Sample collection and processing process are the same with (1)a, (2) About 40 SD Rats, Randomly divided into 2 groups, for each group of 20. Borneol group was given gardenoside and borneol (0.2g·kg-1,ig); Another group as control group separately give gardenoside. Borneol group (0.2g/kg ig, borneol paraffin wax solution), Control solution (liquid paraffin) after 15 min gardenoside rats via tail vein injection solution (300mg·kg-1, iv). Micro rats dialysate collected every 20 minutes at a time, totally of 200 minutes. Each sample (40μL) add 5μL internal standard paeoniflorin (226.8μg/ml) With 135μL regions of the brain a blank micro dialysis mixture dilution, On storage -70℃ to be analysed. (3) About 30 SD Rats, Randomly divided into three groups, for each group of ten only. Blank group and borneol group respectively(0.1,0.2 g/kg, ig), and blank group was given saline 10 ml/kg. Borneol group lavage borneol once a day(0.1,0.2 g/kg). After seven days, Will take off the neck to be put to death for brain in rats, Rapid separation of cortex, hippocampus, striatum, hypothalamus. Then use Western, RT-PCR detection of mdrl in these organizations, mrpl and mrp4, mrp5 expression.Results:(1)a Compared with Borneol of three treatment groups each other, Found Cmax in 15 min of borneol and 30 min group significantly greater than the blank group, It has been clear about the borneol can promote the drugs into the brain. Borneol Cmax and AUCO-up to 15 min group were better than other two group, It Suggests to promote the role of drugs into the brain is one of the most obvious tip of oral drug delivery after 15 min. (1)b Compared with Borneol of four treatment groups each other, Found on the MRT borneol 0.2 g/kg,0.4 g/kg is lower than the other two groups, But in the AUC (0-up), Cmax and CL 0.2g/kg dose group is superior to other groups, This also prompted the promote the drugs into the brain function is one of the most obvious borneol 0.2g/kg dose groups.0.4 g/kg dose group in AUC (0-up), CL and Cmax were second only to 0.2 g/kg dose group, That means just add borneol is dose not improve drugs are produced. (2) In the control group, the AUC (0-t), AUC (0-up) and Cmax in gardenoside content is significantly greater than in other regions of the cortex. Joint for borneol, which results in the hippocampus and hypothalamus gardenoside of AUC (0-T) and Cmax increased, But in the hypothalamus area gardenoside obviously decreased the MRT (0-t), In the cortical, Gardenoside AUC (0-T) and AUC (0-up) seemed as downward trend. (3) Western, RT-PCR test results after to give synthetic borneol, The hippocampus and hypothalamus area of Mrp1/GAPDH, The ratio of Mdr1/GAPDH were significantly lower than the blank group, Tip in the region has a high permeability.Conclusion:(1)a.Borneol 15 min after oral dosing for drugs into the brain of the most obvious. (1)b.Borneol oral dose of 0.2g/kg for the opening of the blood-brain barrier is most obvious. (2) Through micro dialysis-UPLC-MS platform, the method is simple, high sensitivity, good linear, short analysis time, is a kind of efficient method. Applicable to large batch analysis of samples, (3)The expression of mdrl, mrp1 and mrp4, mrp5 different results in different brain regions, Prompted the borneol four areas have different effects on the brain, In the hippocampus and hypothalamus area low expression rate and expression in the cortex and striatum area without obvious difference.