冰片对血脑屏障通透性的双向调节作用影响因素及机制探讨

Effect factors and mechanisms of borneol's bidirectional regulation on blood-brain barrier permeability

有关冰片的研究较多但缺乏规律性总结以及作用机制的深入分析。该文综合整理和分析了近20余年来有关冰片对血脑屏障的影响因素及其作用机制。依据现有研究结果得出如下结论:冰片对血脑屏障通透性影响因素有:(1)不同来源冰片旋光性差异对作用效果无显著影响;(2)冰片剂量在50.00~200.00 mg·kg^(-1)单用或者配伍使用并不影响其作用方向,仅影响其作用强度;(3)冰片单用对生理性血脑屏障能开放其通透性,对病理性血脑屏障能降低其通透性;(4)冰片对于不同大脑疾病模型的血脑屏障,单用或配伍麝香使用均能降低其通透性;(5)冰片配伍黄芪、梓醇、葛根素对病理性血脑屏障通透性有促开放和促进药物透过的作用。冰片对血脑屏障通透性双向调节作用的靶点和机制,与大脑内皮细胞的特殊结构即紧密连接的结构与功能,以及高表达的P-gp外排作用和低胞饮内运作用有关。冰片可通过抑制NF-κB下调P-gp,降低外排作用,提高血脑屏障通透性;也可通过促进血脑屏障胞饮作用,提高血脑屏障通透性;可通过抑制IL-1β,MMP-9表达,对抗其对血管外基膜和紧密连接的降解,降低血脑屏障通透性;通过影响Ca^(2+)-eNOS-NO,VEGF-eNOS-NO等通路对血脑屏障通透性可能具有双向调节作用。冰片调控血脑屏障通透性作用的详细机制较为复杂,有待进一步阐明。

In recent twenty years, there are a lot of studies about the effect of borneol on permeability of blood-brain barrier（BBB） ; however, it is short of regular conclusions of effect factors and in-depth analysis of functional mechanisms. The current researching data were collected and analyzed in this paper for illuminating the effect factors and mechanisms of borneol on permeability of BBB. The fol- lowing conclusions were obtained： five factors about borneol influencing the permeability of BBB. First, opticity activity of borneol had no significant effect on action effects. Second, dose of borneol in the range ofS0. 00-2-0. 00 mg · kg-1 , did not affect the effect direction, but only affect its action intensity either with use alone or combination use. Third, the borneol can increase the permeability of physiological BBB, and decrease the permeability of pathological BBB. Fourth, regardless of using singly or using compatibility with musk, borneol can decrease the permeability of BBB in different brain disease models. Fifth, when used with astragalus, catalpol or puerarin, borneol can increase the permeability of BBB and promote the drugs through BBB in pathological conditions. The target spots and mechanisms of borneol＇s bidirectional regulation on the permeability of BBB are related to the structure and function of cerebral endothelial cells, the exocytosis effects of P-gp and low pinocytosis internal transport effects. On one hand, borneol can down-regulate P-gp by inhibiting NF-KB to reduce the exocytosis effects of P-gp and promote the blood brain barrier pinocytosis to increase the permeability of BBB ; On the other hand, borneol can reduce the degradation of basement membrane of blood vessel and tight junctions by inhibiting the expression of IL-1,8, MMP-9 to decrease the permeability of BBB;moreover, borneol has bidirectional regulation effects on blood-brain barrier permeability by influencing the signaling pathways of Ca2＋ -eNOS-NO, VEGF-eNOS-NO. However, the detailed mechanisms that borneol regulates and controls the permeability of BBB are so complicated, so they shall be further proved and clarified.