超声技术应用于脑疾病治疗的研究进展

Ultrasound application in brain disease treatment:research progress

由于血脑屏障(BBB)的存在,以及脑部缺少明显的增强渗透和滞留效应等因素,脑疾病的有效治疗方法和药物极为有限。超声技术可有效、安全和可逆地打开BBB,是一种理想的实现药物靶向、无创地进入颅内组织的方法,有望在不久的将来成为治疗脑疾病的新手段。本文在介绍脑部递药的一些生物学特点基础上,就超声及其联合微泡技术提高药物靶向脑部递送的机制进行分析,包括紧密连接开放、刺激胞吞作用、抑制多药耐药蛋白表达、提高药物在靶区的浓集并延长滞留时间、调节靶组织的间充质压力等几个方面,然后综述其目前在阿尔茨海默病、亨廷顿舞蹈症、帕金森病、脑肿瘤等疾病治疗中的应用以及存在问题,为进一步改善脑疾病的治疗方案提供参考。

Because of the blood-brain barrier(BBB)and the lack of significant enhancement method for the drug penetration into and retention in brain,effective methods and drugs for the treatment of brain diseases are extremely limited. Ultrasound can effectively,safely and reversibly open the BBB and thus is an ideal method for the targeted,non-invasive drug entry into the intracranial tissue,which has been expected to become a new means for treating brain diseases in the near future. Following a brief introduction of some biological characteristics of brain,this review elaborates the mechanisms of the ultrasound combining microbubbles(USMB)for brain targeted drug delivery,including the opening of the tight junction,stimulation of endocytosis,inhibition of multidrug resistance protein expression,enhancement of drug concentration in target area,extension of the residence time,and adjustment of the interstitial pressure in target tissue. Then,the application of ultrasound in the treatment of some diseases including the Alzheimer′s disease(AD),Huntington′s disease(HD),Parkinson′s disease(PD),and brain tumors are summarized,and the existing problems in the ultrasoundtherapyarealsodiscussed,in order to provide a valuable reference for further improvement in the treatment of brain diseases.