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GYY4137 protects against MCAO via p38 MAPK mediated anti-apoptotic signaling pathways in rats.
Brain Research Bulletin ( IF 3.8 ) Pub Date : 2020-02-27 , DOI: 10.1016/j.brainresbull.2020.02.015
Xu Han 1 , ZhengChun Mao 2 , Shan Wang 1 , Yanming Xin 1 , Ping Li 3 , Surendra Maharjan 3 , Bing Zhang 3
Affiliation  

Hydrogen sulfide (H2S) is a neuromodulator that protect the cerebral ischemia-reperfusion (I/R) injury. The present study aimed to investigate the possible mechanisms of GYY4137 (a slow-releasing donor of H2S) against cerebral I/R injury. GYY4137 significantly increased the level of H2S in rat brain cortex. Compared with the I/R group, the cerebral infarction volume in GYY4137 group (GYY) and SB203580 group (SB) were significantly decreased. Compared with SB group, the cerebral infarction volume in GYY group was significantly decreased. The brain edema in GYY group and SB group were significantly decreased than that in I/R group. Compared with I/R group, the Garcia score in GYY and SB group were significantly increased. Western blot analysis showed that the phosphorylation of p38 MAPK, ERK1/2 and JNK protein in GYY group was significantly increased compared with I/R group. Compared with I/R group, the expression of Bax protein in GYY and SB group were significantly decreased, while the expression of Bcl-2 protein was significantly increased. The activity of caspase-3 in GYY group and SB group were significantly decreased than that of I/R group. Our findings suggested that H2S slow-releasing agent GYY4137 improved the neurological function and reduced the infarct area after cerebral I/R injury. The protective effects were achieved by inhibiting apoptosis via regulating p38 MAPK、ERK1/2 and JNK signaling pathways.

中文翻译:

GYY4137 通过 p38 MAPK 介导的大鼠抗凋亡信号通路防止 MCAO。

硫化氢 (H2S) 是一种保护脑缺血再灌注 (I/R) 损伤的神经调节剂。本研究旨在探讨 GYY4137(一种 H2S 缓释供体)对抗脑 I/R 损伤的可能机制。GYY4137 显着增加大鼠大脑皮层中 H2S 的水平。与I/R组相比,GYY4137组(GYY)和SB203580组(SB)脑梗死体积明显减少。与SB组相比,GYY组脑梗死体积明显减少。GYY组和SB组脑水肿较I/R组明显减轻。与I/R组相比,GYY和SB组Garcia评分显着升高。蛋白质印迹分析表明 p38 MAPK 的磷酸化,GYY组ERK1/2和JNK蛋白较I/R组显着升高。与I/R组相比,GYY和SB组Bax蛋白表达明显降低,Bcl-2蛋白表达明显升高。GYY组和SB组caspase-3活性较I/R组显着降低。我们的研究结果表明 H2S 缓释剂 GYY4137 改善了神经功能并减少了脑 I/R 损伤后的梗死面积。其保护作用是通过调节p38 MAPK、ERK1/2和JNK信号通路抑制细胞凋亡来实现的。GYY组和SB组caspase-3活性较I/R组显着降低。我们的研究结果表明 H2S 缓释剂 GYY4137 改善了神经功能并减少了脑 I/R 损伤后的梗死面积。其保护作用是通过调节p38 MAPK、ERK1/2和JNK信号通路抑制细胞凋亡来实现的。GYY组和SB组caspase-3活性较I/R组显着降低。我们的研究结果表明 H2S 缓释剂 GYY4137 改善了神经功能并减少了脑 I/R 损伤后的梗死面积。其保护作用是通过调节p38 MAPK、ERK1/2和JNK信号通路抑制细胞凋亡来实现的。
更新日期:2020-02-27
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