Protective Effects of Ginkgolide K on Focal Cerebral Ischemia Reperfusion Injury in Rats on the Basis of Amelioration of Mitochondrial Calcium Uniporter
MA Shu-wei1, LIU Xing-yan2, YIN Han-feng3, XIN Yang4, WANG Guo-kang1
1. Traditional Chinese Medicine Institude, Zhejiang Pharmaceutical College, Ningbo 315100, China; 2. Zhejiang Collaborative Innovation Center for High Value Utillization of Byproducts from Ethylene, Ningbo Polytechnic, Ningbo 315800, China; 3. School of Tradition Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China; 4. Institute of Chemistry and Chemical Engineering, Qiqihar University, Qiqihar 161006, China
Abstract：OBJECTIVE To explore whether the protective mechanism of ginkgolide K on cerebral focal ischemia reperfusion injury in rats induced by middle cerebral artery occlusion (MCAO) was associated with the amelioration of mitochondrial calcium uniporter (MCU) or not. METHODS Sprague Dawley (SD) rats were divided into 5 big groups randomly:sham operation group, MCAO group, GK added into RR group, GK group and GK added into SM group. The MCAO rat model were established after cerebral artery ischemia for 2 h and reperfusion for 22 h. Zea Longa 5 score system was used to evaluate neurological deficit score; Determination of brain water content and cerebral infarction areas were determined using gravimetric method and by triphenyltetrazolium chloride(TTC) staining method, respectively. In addition, malondialdehyde (MDA) and superoxide dismutase (SOD), nitric oxide synthase (NOS), nitric oxide (NO) were detected by Elisa. Additionally, mitochondrial i concentration was estimated with the fluorescence spectrophotomete. The morphological change of the injured brains were observed by HE staining. The expression of caspase-3/8/9 protein were detected by Western blot. RESULTS Compared with GK group, GK+RR group relieved obviously the neurological deficit score and reduced the cerebral infarction areas, brain water content, mitochondrial i concentration and MDA, caspase-3/8/9 protein expression while enhance SOD activity. However, the effect of SM on the GK protective activity in MCAO rat injury was the opposite in comparison to GK+RR group. CONCLUSION The stimulative effect of RR and the inhibitory effect of SM on the GK protection in MCAO rat had proves that the protective mechanism of GK on MCAO rat injury is associate with its down-regulation of the transport capacity of MCU, leading the attenuation of mitochondrial i influx.
马舒伟, 刘兴艳, 殷华峰, 辛杨, 王国康. 基于MCU离子通道银杏内酯K对脑缺血再灌注损伤保护作用[J]. 中国药学杂志, 2019, 54(18): 1497-1503.
MA Shu-wei, LIU Xing-yan, YIN Han-feng, XIN Yang, WANG Guo-kang. Protective Effects of Ginkgolide K on Focal Cerebral Ischemia Reperfusion Injury in Rats on the Basis of Amelioration of Mitochondrial Calcium Uniporter. Chinese Pharmaceutical Journal, 2019, 54(18): 1497-1503.
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2019, Vol. 54 
