冰片开放血脑屏障作用与组胺和5-羟色胺的关系

背景:冰片可以可逆性开放血脑屏障,组胺和 5-羟色胺也参与血脑屏障通透性的调节,冰片开放血脑屏障与组胺和 5-羟色胺之间是否存在相关性?目的:观察冰片开放血脑屏障与组胺、5-羟色胺的相关性。设计:完全随机实验。单位:广州中医药大学临床药理研究所。材料:实验于 2003-09/2004-02在广州中医药大学临床药理研究所完成。SD 健康雄性大鼠 104只,由广东省医学实验动物中心提供,体质量230～270g。方法:大鼠随机分为 13组,即药前组和药后组,药后组设高、中、低三个剂量,每个剂量又分为药后 5,20,45,60m in 四个组,每组 8只大鼠。冰片配成 10%粟米油混悬液,实验前夜大鼠禁食过夜,实验当日早晨灌胃给药,高、中、低剂量分别为 0.15,0.12,0.09g/kg。于各时间点采集大鼠下丘脑,制备生物样品,采用高效液相色谱-电化学检测器测定组胺和5-羟色胺的含量。主要观察指标:服冰片后大鼠下丘脑内组胺和 5-羟色胺含量的变化。结果:实验大鼠 104只均进入结果分析。①正常大鼠下丘脑内组胺和5-羟色胺的含量分别为(2.07±0.54)和(1.45±0.14)μg/g。②大鼠服冰片后下丘脑的组胺含量均增高,中剂量药后 20m in 组与药前组比较组胺含量显著升高(3.36±0.21μg/g,P <0.01)],中剂量药后其他各组、高剂量药后 45m in 组、低剂量药后 20和 45m in 组组胺含量显著高于药前组(P <0.05)。③高剂量药后各组 5-羟色胺的含量均比药前组显著升高给药后 5,20,45,60m in 组分别为 (1.90±0.32),(3.28±0.25),(2.66±0.46),(2.80±0.34)μg/g,P <0.05或 P <0.01];中、低剂量药后 5,20,45m in 三组的 5-羟色胺含量显著升高 (P <0.05或 P<0.01)。结论:冰片通过升高大鼠下丘脑组胺和 5-羟色胺的含量,介导血脑屏障的开放。

Relation of openness of blood-brain barrier by borneol with histamine and 5-hydroxytryptamine

BACKGROUND: Borneol can open blood-brain barrier (BBB) but the mechanisms are not very clear. Histamine and 5-hydroxtryptamine can take part in regulation of permeability of BBB. There is not report on the rela tion between the effect of opening BBB of borneol and the regulation of permeability of BBB of histamine (HA)/5-hydroxytryptamine (5-HT). OBJECTIVE: To study the relation between the effect of opening BBB of bornool and the regulation of permeability of BBB of histamine (HA)/5-hydroxytryptamine (5-HT).DESIGN: A completely randomized and controlled study.SETTING: Clinical Pharmacological Institute of University of Traditional Chinese Medicine of Guangzhou.MATERIALS: The experiment was carried out at the Clinical Pharmacological Institute of University of Traditional Chinese Medicine of Guangzhou from September 2003 to February 2004. Totally 104 healthy male SD rats, weighting 230-27.0 g, supplied by Guangdong Medical Experimental Animal Center, were selected.METHODS: The rats were randomly divided into 13 groups: pre-medicine group and post-medicine group (high, moderate and low dosage group and 5, 20, 45 and 60 minutes group in each dosage group) with 8 in each group. Borneol was mixed as 10% millet oil suspension. Rats were fasted before experiment for whole night, and medicine was perfused on the next morning with the high, moderate and low dosage of 0.15, 0.12 and 0.09 g/kg respectively. Hypothalami of rats was selected at various time points to make biological samples. Contents of HA and 5-HT were assayed with HPLC system electrochemical detector.MAIN OUTCOME MEASURES: Changes of level of histamin (HA) and 5-HT in hypothalamus of rats after administration of borneol.RESULTS: Data of totally 104 rats was entered the final analysis. ① Contents of HA and 5-HT in hypothalami were 2.07±0.54 μg/g and 1.45±0.14 μg/g respectively. ② The level of HA in hypothalamus of rats after different doses of borneol were higher than that of before administration. Comparing the level of HA in 20 minutes after moderate dose with before administration, the level of HA in 20 minutes was increased significantly (3.36±0.21) μg/g, P < 0.01], the others of moderate dose, the 45 minutes after high dose, the 20 and 45 minutes after low dose were also increased significantly than before administration (P < 0.05). ③ After administration of different doses of borneol, the level of 5-HT after high dose were higher than that of before administration 5, 20, 45 and 60 minutes after medicine: (1.90±0.32), (3.28 ±0.25), (2.66±0.46), (2.80±0.34) μg/g, respectively; (P < 0.05 or P < 0.01)]; the level of 5-HT after 5, 20 and 45 minutes of moderate and low dose were increased significantly too (P < 0.05 or P < 0.01).CONCLUSION: Borneol could open BBB by increasing levels of HA and 5-HT in hypothalamus of rats.Borneol mediates opening of BBB by increasing levels of HA and5-HT in rats.