目的:观察麝香、安息香和苏合香对血脑屏障(blood-brain barrier,BBB)脑区特异性开放作用及机制。方法:将小鼠分为4组,即麝香组(0.03 g·kg^-1)、苏合香组(0.3 g·kg^-1)、安息香组(0.45 g·kg^-1)和空白组,连续给药7 d后,尾静脉缓慢注射2.5%的伊文思蓝(Evans blue,EB)生理盐水(normal saline,NS)溶液,注射体积0.2 ml·kg^-1,利用紫外荧光酶标仪观察各脑区EB含量。另取大鼠分为麝香组(0.03 g·kg^-1)、苏合香组(0.3 g·kg^-1)、安息香组(0.45 g·kg^-1)和空白组,舌下静脉注射罗丹明123(rhodamine123,Rh123)(0.2 mg·kg^-1),检测各脑区Rh123含量,计算通透指数Kp,并对各脑区进行透射电镜检查,以观察BBB超微结构的改变。结果:与空白组比较,苏合香组可显著提高EB在皮层、海马和下丘脑区域分布,安息香组可显著增加EB在皮层、下丘脑和纹状体区域的分布(P〈0.05,0.01)。与空白组比较,麝香组可显著增加Rh123在海马和下丘脑的分布,苏合香组可显著增加海马和纹状体中Rh123的分布(P〈0.05,0.01)。苏合香组可显著提高海马区域Kp(与空白组比较,P〈0.05)。麝香组、安息香组和苏合香组均不能影响BBB的超微结构。结论:苏合香可引起皮层、海马和下丘脑区域BBB的开放,安息香可引起皮层、下丘脑和纹状体BBB的开放。而麝香并不能引起各脑区BBB的显著开放。苏合香的海马区域开放效应与抑制P-糖蛋白(P-glycoprotein,P-gp)功能有关,而其他药物或苏合香对其他脑区能增加EB的分布可能与Pgp功能和超微结构无关。
OBJECTIVE To observe the opening effects and mechanism of musk,benzoin and styrax on blood-brain barrier brain.METHODS Mice were divided into 4 groups:the musk group(0.03 g·kg^-1),the styrax group(0.3 g·kg^-1),the benzoin group(0.45 g·kg^-1)and the blank group.After the mice were gavaged respectively with musk,benzoin and storax for up to 7 days,2.5% EB with normal saline(0.2 ml·kg^-1)was injected by tail vein.Then the level of EB in brain was studied.Rats were divided into four groups:the musk Group(0.03 g·kg^-1),the storax Group(0.3 g·kg^-1),the benzoin Group(0.45 g·kg^-1)and the blank Group.Rh123(0.2 mg·kg^-1)was given by intravenous injection.Content of Rh123 was determined in different brain areas,and ultrastructural changes of BBB were observed based on the permeability index Kpand examination of transmission electron microscopy.RESULTS Compared with blank group,storax significantly improved distribution of EB in cerebral cortex,hippocampus and hypothalamus,while benzoin significantly increased EB in the cortex,hypothalamus and striatum(P〈0.05,0.01).Compared with blank group,Rh123 content showed that musk evidently promoted distribution of Rh123 in hippocampus and hypothalamus,and storax markedly enhanced Rh123 distribution in Hippocampus and striatum(P〈0.05,0.01).Whereas,storax had promoting effect on Kpin hippocampal region(compared with blank group,P〈0.05).Musk,benzoin and storax could not affect the ultrastructure of BBB.CONCLUSION Storax can promote opening of BBB in cerebral cortex,hippocampus and hypothalamus,while benzoin may stimulate the opening in the cortex,hypothalamus and striatum.Nonetheless,musk has little impacts on the opening of BBB.The opening effects of styrax in hippocampus involve in inhibition of p-glycoprotein function,while other drugs along with styrax increase distribution of EB in other brain areas irrelevant to P-gp function and ultrastructure.