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17β-雌二醇减轻喹啉酸对大鼠海马体的损伤。

17Beta-estradiol attenuates quinolinic acid insult in the rat hippocampus.

作者信息

Heron P, Daya S

机构信息

Division of Pharmacology, Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa.

出版信息

Metab Brain Dis. 2001 Dec;16(3-4):187-98. doi: 10.1023/a:1012593027961.

Abstract

A number of studies have shown that 17beta-estradiol has neuroprotective properties. In this study the neuroprotective effect of 17beta-estradiol against quinolinic-acid-induced neuronal damage was investigated. Ovariectomized rats were separated into three groups of five animals each. Rats received daily subcutaneous injections of either olive oil or 17beta-estradiol in olive oil for 7 days prior to and following a single intrahippocampal injection of 1 micromol quinolinic acid in 2 microL phosphate-buffered saline. The brains were removed and the hippocampi either sectioned and stained for microscopic examination or used in glutamate receptor saturation binding studies. Glutamate receptor displacement binding studies were also performed using concentrations of 0.05 nM-5 microM 17beta-estradiol or quinolinic acid. The results show that 17beta-estradiol protects hippocampal neurons from quinolinic-acid-induced neurodegeneration by competing with quinolinic acid to bind to the N-methyl-D-aspartate (NMDA) receptor. This would result in a decrease in intracellular free-calcium influx and resultant neuronal swelling.

摘要

多项研究表明,17β-雌二醇具有神经保护特性。在本研究中,对17β-雌二醇抗喹啉酸诱导的神经元损伤的神经保护作用进行了研究。将去卵巢大鼠分为三组,每组五只动物。在单次海马内注射溶于2微升磷酸盐缓冲盐水中的1微摩尔喹啉酸之前和之后7天,大鼠每天皮下注射橄榄油或溶于橄榄油中的17β-雌二醇。取出大脑,将海马体切片并染色以进行显微镜检查,或将其用于谷氨酸受体饱和结合研究。还使用0.05 nM - 5 microM的17β-雌二醇或喹啉酸浓度进行了谷氨酸受体置换结合研究。结果表明,17β-雌二醇通过与喹啉酸竞争结合N-甲基-D-天冬氨酸(NMDA)受体,保护海马神经元免受喹啉酸诱导的神经变性。这将导致细胞内游离钙内流减少以及由此产生的神经元肿胀。

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