Baicalin attenuates in vivo and in vitro hyperglycemia-exacerbated ischemia/reperfusion injury by regulating mitochondrial function in a manner dependent on AMPK

被引：97
作者：
Li, Shanshan [1 ,2 ]
Sun, Xiaoxu [1 ,2 ]
Xu, Lixing [1 ,2 ]
Sun, Ruoxi [1 ,2 ]
Ma, Zhanqiang [1 ,2 ]
Deng, Xueyang [1 ,2 ]
Liu, Baolin [1 ,2 ]
Fu, Qiang [1 ,2 ]
Qu, Rong [3 ]
Ma, Shiping [1 ,2 ]
机构：
[1] China Pharmaceut Univ, Dept Pharmacol Chinese Mat Med, 639 Longmian Rd, Nanjing 211198, Jiangsu, Peoples R China
[2] China Pharmaceut Univ, Jiangsu Prov Key Lab TCM Evaluat & Translat Res, 639 Longmian Rd, Nanjing 211198, Jiangsu, Peoples R China
[3] Nanjing Univ Tradit Chinese Med, Dept Pharmacol Tradit Chinese Med Formulae, 138 Xianlin Rd, Nanjing 210029, Jiangsu, Peoples R China
来源：
EUROPEAN JOURNAL OF PHARMACOLOGY | 2017年 / 815卷
基金：
中国国家自然科学基金;
关键词：
AMPK; Baicalin; Mitochondrial dynamic; Apoptosis; Mitophagy; CEREBRAL ISCHEMIA-REPERFUSION; ACTIVATED PROTEIN-KINASE; INDUCED AUTOPHAGY; NEURONAL DEATH; MITOFUSIN; CELL-DEATH; STRESS; APOPTOSIS; DYNAMICS; DYSFUNCTION;
D O I：
10.1016/j.ejphar.2017.07.041
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Cerebral ischemia/reperfusion (I/R) is a lethal and disabling disease. Studies have suggested that hyperglycemia is a risk factor for cerebral I/R. Baicalin is a natural bioactive flavonoid extracted from Scutellaria baicalensis Georgi with neuroprotective activity. In the present study, we investigated the effects of baicalin on hyperglycemia-exacerbated cerebral I/R injury. Streptozotocin (STZ) injection aggravated the brain damage induced by middle cerebral artery occlusion (MCAO) surgery, while baicalin administration reduced blood glucose, relieved neurological deficit and decreased infarct volume. In vitro, Oxygen-glucose deprivation/reperfusion (OGD/REP) induced inordinate reactive oxygen species (ROS) production and mitochondrial dynamic impairments were markedly increased under high glucose (HG) condition. Baicalin treatment in PC12 cells inhibited dynamin-related protein 1 (Drp-1) expression, decreased mitochondrial fission, promoted mitofusin-2 (MFN2) generation, increased Drp-1 Ser637 phosphorylation, and elevated mitochondrial membrane potential (Delta psi m) via the suppression of ROS production. However, AMPK alpha 1 knockdown abolished the protective effects of baicalin. Baicalin also suppressed cell apoptosis and enhanced mitophagy. These results suggested that baicalin protected against hyperglycemia aggravated I/R injury by regulating mitochondrial functions in a manner dependent on AMPK.
引用
收藏
页码：118 / 126
页数：9
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