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一种用于监测脑细胞外葡萄糖的安培型葡萄糖氧化酶/聚(邻苯二胺)生物传感器:在自由活动大鼠纹状体中的体内表征

An amperometric glucose-oxidase/poly(o-phenylenediamine) biosensor for monitoring brain extracellular glucose: in vivo characterisation in the striatum of freely-moving rats.

作者信息

Lowry J P, Miele M, O'Neill R D, Boutelle M G, Fillenz M

机构信息

University laboratory of Physiology, Oxford, UK.

出版信息

J Neurosci Methods. 1998 Jan 31;79(1):65-74. doi: 10.1016/s0165-0270(97)00171-4.

DOI:10.1016/s0165-0270(97)00171-4
PMID:9531461
Abstract

Amperometric glucose biosensors based on the immobilization of glucose oxidase (GOx) on Pt electrodes with electropolymerized o-phenylenediamine (PPD) were implanted in the right striatum of freely-moving rats. Carbon paste electrodes for the simultaneous monitoring of ascorbic acid (AA) and/or tissue O2 were implanted in the left striatum. A detailed in vivo characterization of the Pt/PPD/GOx signal was carried out using various pharmacological manipulations. Confirmation that the biosensor responded to changing glucose levels in brain extracellular fluid (ECF) was obtained by intraperitoneal (i.p.) injection of insulin that caused a decrease in the Pt/PPD/GOx current, and local administration of glucose (1 mM) via an adjacent microdialysis probe that resulted in an increase in the biosensor current. An insulin induced increase in tissue O2 in the brain was also observed. Interference studies involved administering AA and subanaesthetic doses of ketamine i.p. Both resulted in increased extracellular AA levels with ketamine also causing an increase in O2. No significant change in the Pt/PPD/GOx current was observed in either case indicating that changes in O2 and AA, the principal endogenous interferents, have minimal effect on the response of these first generation biosensors. Stability tests over a successive 5-day period revealed no significant change in sensitivity. These in vivo results suggest reliable glucose monitoring in brain ECF.

摘要

将基于葡萄糖氧化酶(GOx)固定在经电聚合邻苯二胺(PPD)修饰的铂电极上的安培型葡萄糖生物传感器植入自由活动大鼠的右纹状体。将用于同时监测抗坏血酸(AA)和/或组织氧的碳糊电极植入左纹状体。使用各种药理学操作对铂/PPD/GOx信号进行了详细的体内表征。通过腹腔注射胰岛素导致铂/PPD/GOx电流降低,以及通过相邻的微透析探针局部给予葡萄糖(1 mM)导致生物传感器电流增加,证实了生物传感器对脑细胞外液(ECF)中葡萄糖水平变化有响应。还观察到胰岛素诱导脑内组织氧增加。干扰研究包括腹腔注射AA和亚麻醉剂量的氯胺酮。两者均导致细胞外AA水平升高,氯胺酮还导致氧增加。在这两种情况下,铂/PPD/GOx电流均未观察到显著变化,表明主要内源性干扰物氧和AA的变化对这些第一代生物传感器的响应影响最小。连续5天的稳定性测试显示灵敏度无显著变化。这些体内结果表明可在脑ECF中进行可靠的葡萄糖监测。

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