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G protein-coupled estrogen receptor alleviates cerebral ischemia-reperfusion injury through inhibiting endoplasmic reticulum stress

HAN Zi-Wei, ZHU Li-Cang, CHANG Yue-Chen, ZHOU Ying, ZONG Jia-An, MA Ke-Tao, SI Jun-Qiang, LI Li^*

Department of Physiology, Shihezi University Medical College/Xinjiang Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, Shihezi 832002, China

Abstract

The aim of this study was to investigate whether G protein-coupled estrogen receptor (GPER) could alleviate hippocampal neuron injury under cerebral ischemia-reperfusion injury (CIRI) by acting on endoplasmic reticulum stress (ERS). The CIRI animal model was established by middle cerebral artery occlusion (MCAO). Female ovariectomized (OVX) Sprague-Dawley (SD) female rats were randomly divided into 4 groups: control, ischemia-reperfusion injury (MCAO), vehicle (MCAO+DMSO), and GPER-specific agonist G1 (MCAO+G1) groups. The neurobehavioral score was assessed by the Longa score method, the morphological changes of the neurons were observed by the Nissl staining, the cerebral infarction was detected by the TTC staining, and the neural apoptosis in the hippocampal CA1 region was detected by TUNEL staining. The distribution and expression of GRP78 (78 kDa glucose-regulated protein 78) in the hippocampal CA1 region were observed by immunofluorescent staining. The protein expression levels of GRP78, Caspase-12, CHOP and Caspase-3 were detected by Western blot, and the mRNA expression levels of GRP78, Caspase-12, and CHOP were detected by the real-time PCR. The results showed that the neurobehavioral score, cerebral infarct volume, cellular apoptosis index, as well as GRP78, Caspase-12 and CHOP protein and mRNA expression levels in the MCAO group were significantly higher than those of control group. And G1 reversed the above-mentioned changes in the MCAO+G1 group. These results suggest that the activation of GPER can decrease the apoptosis of hippocampal neurons and relieve CIRI, and its mechanism may involve the inhibition of ERS.

Key words: G protein-coupled estrogen receptor; apoptosis; endoplasmic reticulum stress; post-treatment; cerebral ischemia-reperfusion injury

Received: 2018-10-24　　Accepted: 2018-12-15

Corresponding author: 李丽　　E-mail: 577840908@qq.com

DOI: 10.13294/j.aps.2019.0054

Citing This Article：

HAN Zi-Wei, ZHU Li-Cang, CHANG Yue-Chen, ZHOU Ying, ZONG Jia-An, MA Ke-Tao, SI Jun-Qiang, LI Li. G protein-coupled estrogen receptor alleviates cerebral ischemia-reperfusion injury through inhibiting endoplasmic reticulum stress. Acta Physiol Sin 2019; 71 (4): 527-536 (in Chinese with English abstract).