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四羟基二苯乙烯葡萄糖苷通过抑制NADPH氧化应激减轻小鼠脑缺血/再灌注损伤诱导的细胞凋亡和自噬

Tetrahydroxystilbene Glucoside Suppresses NAPDH Oxidative Stress to Mitigate Apoptosis and Autophagy Induced by Cerebral Ischemia/Reperfusion Injury in Mice.

作者信息

Yu Feng, Xue Wei, Dong Liuyi, Hu Xiangyang, Huang Dake, Wang Kai

机构信息

Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.

Department of Neurology, Anhui Provincial Hospital, Hefei 230001, China.

出版信息

Evid Based Complement Alternat Med. 2019 Jul 17;2019:3913981. doi: 10.1155/2019/3913981. eCollection 2019.

Abstract

Tetrahydroxystilbene glucoside (TSG) is the active ingredient extracted from the traditional Chinese medicine , which has extensive pharmacological activities. The current study aimed to observe the neuroprotective mechanism of TSG in the ischemia/reperfusion (I/R) brain injury-induced apoptosis and autophagy from the point of view of oxidative stress (OS). The middle cerebral artery occlusion (MCAO) model was prepared through the suture-occluded method, and TSG was administered through tail vein injection at the time of reperfusion at the doses of 3.0, 6.0, and 12.0 mg/kg. Compared with sham group, the neurological score in I/R mice was increased (P<0.05), along with remarkably elevated cerebral infarct volume (P<0.05); while TSG administration could reduce the neurological score and cerebral infarct volume (P<0.05) and improve the neuronal damage in ischemic cortex and hippocampus (P<0.05). The expression of NOX4, activated caspase-3(9), and Beclin 1 (P<0.05), as well as the LC3BII/I ratio, had been markedly elevated (P<0.05), while TSG administration could effectively suppress the expression of the above-mentioned proteins (P<0.05). In conclusion, TSG shows obvious protection against brain injury in I/R mice, and its mechanism may be related to suppressing the NADPH-induced OS and reducing neuronal apoptosis as well as autophagy.

摘要

四羟基二苯乙烯苷(TSG)是从中药中提取的活性成分,具有广泛的药理活性。本研究旨在从氧化应激(OS)角度观察TSG对缺血/再灌注(I/R)脑损伤诱导的细胞凋亡和自噬的神经保护机制。采用线栓法制备大脑中动脉闭塞(MCAO)模型,并在再灌注时通过尾静脉注射给予TSG,剂量分别为3.0、6.0和12.0mg/kg。与假手术组相比,I/R小鼠的神经功能评分升高(P<0.05),脑梗死体积也显著增大(P<0.05);而给予TSG可降低神经功能评分和脑梗死体积(P<0.05),并改善缺血皮层和海马区的神经元损伤(P<0.05)。NOX4、活化的caspase-3(9)和Beclin 1的表达(P<0.05)以及LC3BII/I比值均显著升高(P<0.05),而给予TSG可有效抑制上述蛋白的表达(P<0.05)。综上所述,TSG对I/R小鼠脑损伤具有明显的保护作用,其机制可能与抑制NADPH诱导的OS、减少神经元凋亡和自噬有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ba/6662418/2a774b3a1585/ECAM2019-3913981.001.jpg

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