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通过微透析监测大鼠脑内反复全脑缺血和继发性低氧血症时的细胞外缺血标志物

Extracellular ischaemia markers in repeated global ischaemia and secondary hypoxaemia monitored by microdialysis in rat brain.

作者信息

Valtysson J, Persson L, Hillered L

机构信息

Department of Neurosurgery, Uppsala University Hospital, Sweden.

出版信息

Acta Neurochir (Wien). 1998;140(4):387-95. doi: 10.1007/s007010050113.

DOI:10.1007/s007010050113
PMID:9689331
Abstract

The aim of this study was to explore the usefulness of extracellular markers of cerebral ischaemia. Cortical microdialysate concentrations of the energy related metabolites lactate, pyruvate, glucose, adenosine, inosine, hypoxanthine and xanthine, were measured in rats subjected to repeated transient ischaemia. The animals were subjected to one or two 10-min periods of global ischaemia produced by induced intracranial hypertension, with a 2 h period of reperfusion after each insult. In addition, the effect of superimposed secondary hypoxaemia and hypotension was studied. In general, there was a good agreement between the extracellular markers and known intracellular energy disturbances under similar conditions, including marked transient increases of lactate, lactate/pyruvate ratio, inosine and hypoxanthine. Several new observations were made: (1) glucose appeared to be a useful marker of severe ischaemia and recirculation, (2) a marked post-ischaemic xanthine formation was observed implicating a substantial loss of salvageable hypoxanthine as well as increased production of superoxide radicals, (3) a blunted purine response was noted after the second insult, reflecting a reduced intracellular adenine nucleotide pool, and (4) a different pattern of ischaemia markers was observed during secondary hypoxia as compared to hypoxia with hypotension. In conclusion, extracellular lactate, pyruvate, glucose, adenosine, inosine hypoxanthine and xanthine all seem valuable as ischaemia markers. The results support the usefulness of intracerebral microdialysis for monitoring of energy metabolic disturbances caused by cerebral ischaemia/hypoxia. The pattern of extracellular ischaemia markers may help differentiate between various causes of energy perturbations, such as different degrees of ischaemia and hypoxia.

摘要

本研究的目的是探讨脑缺血细胞外标志物的作用。在经历反复短暂缺血的大鼠中,测量了与能量相关的代谢物乳酸、丙酮酸、葡萄糖、腺苷、肌苷、次黄嘌呤和黄嘌呤的皮质微透析液浓度。通过诱导颅内高压使动物经历一或两个10分钟的全脑缺血期,每次缺血后有2小时的再灌注期。此外,还研究了叠加的继发性低氧血症和低血压的影响。一般来说,在相似条件下,细胞外标志物与已知的细胞内能量紊乱情况有很好的一致性,包括乳酸、乳酸/丙酮酸比值、肌苷和次黄嘌呤的明显短暂升高。有几项新的观察结果:(1)葡萄糖似乎是严重缺血和再灌注的有用标志物;(2)观察到缺血后黄嘌呤明显形成,这意味着可挽救的次黄嘌呤大量损失以及超氧自由基产生增加;(3)第二次缺血后嘌呤反应减弱,反映细胞内腺嘌呤核苷酸池减少;(4)与低氧合并低血压相比,继发性低氧血症期间观察到不同的缺血标志物模式。总之,细胞外乳酸、丙酮酸、葡萄糖、腺苷、肌苷、次黄嘌呤和黄嘌呤似乎都是有价值的缺血标志物。这些结果支持脑内微透析在监测脑缺血/低氧引起的能量代谢紊乱方面的作用。细胞外缺血标志物模式可能有助于区分能量紊乱的各种原因,如不同程度的缺血和低氧。

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