Tanshinone IIA attenuates neuronal damage and the impairment of long-term potentiation induced by hydrogen peroxide
Tanshinone IIA attenuates neuronal damage and the impairment of long-term potentiation induced by hydrogen peroxide
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丹参酮 IIA 减轻过氧化氢引起的神经元损伤和长时程增强损伤
DOI：
10.1016/j.jep.2010.11.069
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发表时间：
2011-03-08
影响因子：
5.4
通讯作者：
Chen, Jian-Guo
中科院分区：
文献类型：
--
作者：
Wang, Wei;Zheng, Li-Li;Chen, Jian-Guo
研究目的：丹参酮Ⅱ A（Tanshinone IIA，Tan IIA）是丹参的主要成分之一，在亚洲国家被广泛用于治疗各种心脑血管疾病。许多研究已经报道了Tan IIA具有抗氧化特性，但Tan IIA是否能拯救神经元免受氧化损伤还未见报道。材料与方法：采用细胞MTT法和PI染色流式细胞术检测H2 O2对大鼠神经细胞的毒性作用。采用钙离子成像技术测定细胞内游离钙离子浓度。Western blotting检测Bax、Bcl-2蛋白表达。采用海马脑片电生理方法，观察Tan IIA对H2 O2所致大鼠海马神经元突触功能和认知功能损害的影响。结果：Tan HA预处理可保护原代大鼠皮层神经元免受H2 O2的损伤。Tan Ⅱ A还能显著降低H_2O_2引起的[Ca ~（2+）]（i）升高。蛋白质印迹分析表明，Tan HA预处理可以阻止H2 O2诱导的Bax/Bcl-2比值的增加。此外，Tan IIA预孵育前20分钟H2 O2暴露可以逆转H2 O2诱导的海马LTP损伤，但没有显着改变基础突触传递和LTP induction.Conclusions：这些研究结果表明，Tan IIA可能作为一种新的有前途的治疗剂氧化应激损伤的神经退行性疾病。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Aim of the study: Tanshinone IIA (Tan IIA) is one of the key components of Salvia miltiorrhiza Bunge that has been widely used for various cardiovascular and cerebrovascular disorders in Asian countries. Many studies have reported that Tan IIA has antioxidative properties, but whether Tan IIA can rescue neurons from oxidative insult has never been reported. The present study was undertaken to evaluate the possible neuroprotective effects of Tan IIA on hydrogen peroxide (H2O2)-induced oxidative stress in rats.Materials and methods: H2O2-induced cytotoxicity was evaluated by the cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and flow cytometry with PI staining. Calcium imaging experiments were carried out to measure intracellular free calcium concentration. Western blotting was used to determine the expression of Bax and Bcl-2 protein. Electrophysiological studies in hippocampal slices were performed to investigate the effect of Tan IIA on synaptic function and cognitive impairment caused by H2O2.Results: It was found that pretreatment with Tan HA protected primary rat cortical neurons against H2O2-induced cytotoxicity. Furthermore, Tan IIA markedly reduced the elevation of [Ca2+](i) evoked by H2O2. Western blot analysis indicated that pretreatment with Tan HA prevented the increase in Bax/Bcl-2 ratio induced by H2O2. In addition, preincubation of Tan IIA 20 min prior to H2O2 exposure could reverse H2O2-induced hippocampal LTP impairment, but without significant alteration in basal synaptic transmission and LTP induction.Conclusions: These findings demonstrate that Tan IIA might serve as a novel promising therapeutic agent for oxidative stress injury in neurodegenerative diseases. (C) 2010 Elsevier Ireland Ltd. All rights reserved.