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盐酸戊乙奎醚对心肌细胞缺氧/复氧损伤的后适应保护作用。

Postconditioning Protection Against Myocardiocyte Anoxia/Reoxygenation Injury From Penehyclidine Hydrochloride.

作者信息

Ren J Y, Lin D M, Wang C B, Yang Y L, Wang Z Q, Cui B Q, Ma J

机构信息

Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, People's Republic of China.

出版信息

Drug Des Devel Ther. 2019 Nov 26;13:3977-3988. doi: 10.2147/DDDT.S224282. eCollection 2019.

DOI:10.2147/DDDT.S224282
PMID:32063699
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6884978/
Abstract

BACKGROUND/AIMS: To investigate the postconditioning protective effect of penehyclidine hydrochloride (PHC) against anoxia/reoxygenation (A/R) injury in H9c2 cells along with the involved mechanism and timing effect.

METHODS

We divided H9c2 cells into 7 groups: control group, A/R group and PHC+A/R groups at 0 min, 5 mins, 10 mins, 20 mins, 30 mins, respectively (treated with 0.1 μm/L PHC at 0 min, 5 mins, 10 mins, 20 mins, 30 mins after the reoxygenation procedure began). Cell apoptosis, oxidative stress, intracellular Ca concentration, mitochondrial membrane potential and mitochondrial permeability transition pore (MPTP) opening were explored. Bcl-2, Bax, Cyt C, caspase-3 and caspase-9 levels were measured.

RESULTS

A/R significantly increased both cell injury and cell apoptosis. PHC showed postconditioning protective effect by attenuating superoxide production, decreasing Ca overload, restraining MPTP activities, restoring mitochondrial membrane potential, regulating cell apoptosis proteins and modulation of mitochondrial pathway. Earlier administration of PHC offered greater postconditioning protective effect.

CONCLUSION

H9c2 cells were protected by PHC from A/R injury regardless of timing of PHC administration (0 min, 5 mins, 10 mins, 20 mins, 30 mins). However, earlier administration of PHC resulted in better PHC postconditioning protection.

摘要

背景/目的:研究盐酸戊乙奎醚(PHC)对H9c2细胞缺氧/复氧(A/R)损伤的后适应保护作用及其相关机制和时效关系。

方法

将H9c2细胞分为7组:对照组、A/R组以及分别在复氧开始后0分钟、5分钟、10分钟、20分钟、30分钟给予PHC的PHC+A/R组(均用0.1μm/L PHC处理)。检测细胞凋亡、氧化应激、细胞内钙浓度、线粒体膜电位及线粒体通透性转换孔(MPTP)开放情况。测定Bcl-2、Bax、Cyt C、caspase-3和caspase-9水平。

结果

A/R显著增加细胞损伤和细胞凋亡。PHC通过减轻超氧化物生成、降低钙超载、抑制MPTP活性、恢复线粒体膜电位、调节细胞凋亡蛋白以及调控线粒体途径发挥后适应保护作用。更早给予PHC后适应保护作用更强。

结论

无论PHC给药时间(0分钟、5分钟、10分钟、20分钟、30分钟)如何,PHC均可保护H9c2细胞免受A/R损伤。然而,更早给予PHC可产生更好的后适应保护效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8d8/6884978/d34d7a60fda4/DDDT-13-3977-g0010.jpg
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