丹参酮ⅡA通过改善线粒体功能和氧化应激减轻大鼠认知障碍

TanshinoneⅡA Attenuates Cognitive Impairment in Rats via Improving Mitochondrial Function and Oxidative Stress

通过建立双侧颈总动脉结扎(BCCAO)大鼠模型和H_2O_2诱导的原代星形胶质细胞的氧化损伤模型,探究丹参酮ⅡA(TSA)的神经保护作用和机制。TSA逆转了BCCAO诱导的大鼠认知障碍和神经元丢失,增加了皮层和海马中脑源性神经营养因子(BDNF)的表达。TSA抑制了细胞活力的降低和乳酸脱氢酶(LDH)的释放。其次,TSA减弱了线粒体膜电位(MMP)的丧失,并增加了三磷酸腺苷(ATP)水平。TSA显著逆转了由线粒体复合酶异常引起的损伤,降低了活性氧(ROS)积累和脂质过氧化水平,同时增强了抗氧化能力。研究表明,TSA可以增强线粒体生物能并有效减轻氧化损伤,发挥神经保护作用。

Chronic cerebral hypoperfusion(CCH)is one of the most important causes in the initiation and progression of vascular dementia.TanshinoneⅡA(TSA)is an active compound isolated from the plant roots of Salvia Miltiorrhiza,which is a traditional Chinese medicine with the activities of improving blood circulation and reducing vessel stasis.In this study,the potential neuroprotective effects and mechanisms of TSA were studied using a bilateral common carotid artery occlusion(BCCAO)model in vivo and H2O2 induced oxidative damage of primary astrocytes in vitro.The results showed that TSA obviously reversed the BCCAO induced cognitive impairment in rats evaluated by Morris water maze(MWM).Nissl staining showed the neuronal loss in CA1 and CA3 region were reversed by TSA.TSA also increased the expression of brain-derived neurotrophic factor(BDNF)levels in cortex and hippocampus.In H2O2-induced primary astrocytes injury,TSA suppressed the decrease of cell viability and inhibited lactate dehydrogenase(LDH)release.TSA attenuated mitochondrial membrane potential(MMP)loss and increased ATP level.Furthermore,TSA significantly reversed the damage induced by the disorders of the mitochondria respiratory complex enzyme,and then attenuated reactive oxygen species(ROS)accumulation and lipid peroxidation,simultaneously enhanced antioxidant capacity.The results demonstrated that TSA could enhance mitochondrial bioenergetics and ameliorate oxidative stress effectively,which might contribute to the improving effect of TSA on cerebral ischemia,hypoperfusion and oxidative injuries.Our study provided a new evidence to illustrate the mechanisms of protective effects of TSA on cerebral ischemia induced cognitive impairment.