Yu Ting, Li Lei, Bi Yanwen, Liu Zhen, Liu Huaxiang, Li Zhenzhong
Department of Anatomy, Shandong University School of Medicine, Shandong, China.
J Pharm Pharmacol. 2014 Aug;66(8):1150-60. doi: 10.1111/jphp.12244. Epub 2014 Mar 27.
High glucose-evoked oxidative stress and apoptosis within Schwann cells (SCs) are mechanisms facilitating the procession of diabetic peripheral neuropathy (DPN). Although erythropoietin (EPO) was demonstrated to have neuroprotective effects in neurodegenerative diseases, the effects of EPO on glucose-evoked oxidative stress and apoptosis of SCs remain unknown.
Primary cultured SCs isolated from streptozotocin (STZ)-induced diabetic peripheral neuropathic rats and normal control rats were exposed to high or normal glucose condition with or without EPO incubation for 72 h. Cell viability, apoptotic rate, cellular reactive oxygen species (ROS) level, total glutathione (GSH) level, EPO mRNA and erythropoietin receptor (EPOR) mRNA levels were assayed.
SCs from diabetic rats showed a lower cell viability and a higher apoptotic rate. High glucose culture condition elevated ROS level and diminished total GSH level of SCs. EPO improved cell viability and decreased cell apoptotic rate of SCs. EPO also elevated total GSH level and decreased intracellular ROS level. SCs from diabetic rats exhibited higher EPO mRNA and EPOR mRNA levels than SCs from normal control rats.
The data of this study offered fresh viewpoints for interpreting the pathogenesis of DPN and novel pharmacological principles implicit in the therapeutic effect of EPO.
雪旺细胞(SCs)内高糖诱发的氧化应激和凋亡是促进糖尿病周围神经病变(DPN)进展的机制。尽管已证明促红细胞生成素(EPO)在神经退行性疾病中具有神经保护作用,但EPO对高糖诱发的SCs氧化应激和凋亡的影响仍不清楚。
将从链脲佐菌素(STZ)诱导的糖尿病周围神经病变大鼠和正常对照大鼠分离的原代培养SCs暴露于高糖或正常糖条件下,分别进行有无EPO孵育72小时。检测细胞活力、凋亡率、细胞活性氧(ROS)水平、总谷胱甘肽(GSH)水平、EPO mRNA和促红细胞生成素受体(EPOR)mRNA水平。
糖尿病大鼠的SCs显示出较低的细胞活力和较高的凋亡率。高糖培养条件提高了SCs的ROS水平并降低了总GSH水平。EPO改善了SCs的细胞活力并降低了细胞凋亡率。EPO还提高了总GSH水平并降低了细胞内ROS水平。糖尿病大鼠的SCs比正常对照大鼠的SCs表现出更高的EPO mRNA和EPOR mRNA水平。
本研究的数据为解释DPN的发病机制提供了新的观点,并为EPO治疗作用中隐含的新药理学原理提供了依据。