维生素C在脑病理损伤模型中变化规律的研究进展

Recent studies on dynamics of vitamin C during some pathological injury models

维生素C是生命体内不可或缺的水溶性维生素,因其具有防治坏血病的作用,故又被称为抗坏血酸(ascorbic acid,AA).在脑神经系统中,AA是重要的小分子化学物质之一,其作为抗氧化剂和神经调质,在脑神经生理与病理过程中发挥着重要的作用.尽管人们在很早即开展了AA脑神经生理和病理作用的探索,但是其神经化学机制,尤其是在脑损伤过程的变化规律,仍需进一步研究.在生理溶液中,AA易被化学氧化,故不稳定.这一特点也决定了传统分析化学方法难以实现脑内AA的准确测定.这一检测方法的困难极大限制了AA神经化学机制的研究.因此,建立和发展具有时空分辨、高灵敏、高选择的分析化学原理和方法,实现活体层次AA的传感分析,无疑会大大推动AA神经化学机制的研究.针对AA活体分析中存在的挑战,利用电化学原理,本课题组已经发展了基于微透析技术的活体在线电化学方法和活体原位电化学传感方法等,实现了一些生理病理过程中AA变化规律的研究.本文将主要围绕本课题组近些年来在这一方面的研究展开综述.

As one of the small molecules in brain,Vitamin C(ascorbic acid,AA)exerts a wide array of biochemical reactions.It is considered critical for scavenging endogenously generated free radicals,serving as one of the most important neuroprotectors for various oxidative stress-associated brain dysfunctions such as cerebral ischemia injury,epilepsy and Parkinson’s disease.AA is also considered as sort of neuromodulator and cofactor of enzymes involved in both the synthesis of neurotransmitters and the modulation of glutamate mediated neurotransmission.Although the physiological and pathological functions of AA have been explored since the 1970 s,the dynamics of AA in the processes of brain injury remain largely unknown.This review mainly summarizes our recent findings on the dynamics of AA in the processes of brain injury enabled by in vivo electrochemical sensing methods developed in our laboratory.AA,a hexonic sugar acid,has two dissociable protons(p Ka4.04 and 11.34).In chemistry,AA is unstable and easily oxidizable in physiological solutions,which renders difficulties in in vitro sensing of AA in the central nervous system(CNS)with conventional analytical methods.Such an analytical challenge unfortunately offers a barrier to understand the neurochemical mechanism of AA.From fundamental electrochemistry viewpoint,AA can be electrochemically oxidized through a two-electron and one-proton pathway under neutral conditions.The adsorption of product 2,3-diketogulanic acid on electrode surface leads to electrode fouling and further generates high overpotential for the oxidation process.This intrinsic feature unfortunately invalidates the direct use of electrochemical property of AA to develop an electrochemical sensor for in vivo selective sensing of AA in rat brain.At most carbon electrodes,AA is an inner-sphere redox species with electron-transfer kinetics sensitive to the nature of the electrode surface.Thus,tuning surface chemistry of electrode would provide an effective strategy for the acceleration of electron-transfer kinetics of the oxidation of AA.To this end,pre-treatment of carbon electrodes can promote a large increase in the electrode activity for the oxidation of AA;however,it remains practically difficult to reproducibly produce the same surface chemistry at the preactivated electrodes even under the same conditions.Therefore,electrocatalysis is another important approach to efficiently enhance the electron transfer kinetics of AA oxidation that achieves the selectivity for in vivo AA sensing.Along with this line,our group have engaged into the development of electrochemical methods by modulation of electron transfer kinetics of AA oxidation.We have found that,with carbon nanotubes(CNTs)as electrode,the oxidation of AA can be greatly enhanced.Based on this finding,we have successfully developed CNT-based online electrochemical system(OECS)and in vivo sensing system(with CNT-modified carbon fiber electrode).This review mainly focuses on the recent advances(most from our group)in the studies on the dynamics of AA in some brain injury models,promoting the understanding on the neurochemical processes related with AA,such as glutamate excitotoxicity and oxidative stress.