谷胱甘肽通过 Akt 通路防止游离脂肪酸诱导的人脑血管内皮细胞氧化应激和细胞凋亡。
Glutathione prevents free fatty acids-induced oxidative stress and apoptosis in human brain vascular endothelial cells through Akt pathway.
机构信息
Department of Geriatrics Neurology, Huashan Hospital, Fudan University, Shanghai, China.
出版信息
CNS Neurosci Ther. 2013 Apr;19(4):252-61. doi: 10.1111/cns.12068.
AIMS
The damage of human brain vascular endothelial cells (HBVECs) is the key pathogenesis of diabetes-associated cerebral vascular complications. The aim of this study was to elucidate the effects of glutathione (GSH) on free fatty acids (FFAs)-induced HBVECs apoptosis, oxidative stress, and the involved possible signaling pathway.
METHODS
After culturing HBVECs for 72 h with GSH and FFAs, we determined cell proliferation by CCK8, detected apoptosis by caspase-3 and Annexin V-FITC/PI staining, and judged oxygen stress by determining the reactive oxygen species (ROS) and the mitochondrial membrane potential (MMP). We investigated whether the Akt pathway was involved in FFAs-induced signaling pathway alteration and whether GSH influenced the above effects.
RESULTS
After being cultured in 200 μM FFAs for 72 h, the HBVECs proliferation significantly decreased; HBVECs apoptosis increased; the ROS levels increased; and the HBVECs MMP subsequently decreased. FFAs induced a significant decrease in phosphorylated active Akt. These alterations were obviously prevented when 1 mM GSH was added to culture medium containing FFAs, and the above effects of GSH were blocked by Akt inhibitor.
CONCLUSION
GSH may prevent FFAs-induced HBVECs damage, oxidative stress, and apoptosis through activating the Akt pathway.
目的
人脑血管内皮细胞（HBVEC）的损伤是糖尿病相关脑血管并发症的关键发病机制。本研究旨在阐明谷胱甘肽（GSH）对游离脂肪酸（FFAs）诱导的HBVEC 细胞凋亡、氧化应激的影响及其可能涉及的信号通路。
方法
用 GSH 和 FFAs 培养 HBVEC 72 h 后，用 CCK8 法测定细胞增殖，用 caspase-3 和 Annexin V-FITC/PI 染色法检测细胞凋亡，用测定活性氧（ROS）和线粒体膜电位（MMP）判断氧应激。研究 Akt 通路是否参与 FFAs 诱导的信号通路改变，以及 GSH 是否影响上述作用。
结果
用 200 μM FFAs 培养 72 h 后，HBVEC 增殖明显减少；HBVEC 凋亡增加；ROS 水平升高；随后 HBVECs 的 MMP 降低。FFAs 诱导磷酸化活性 Akt 明显减少。当向含 FFAs 的培养基中加入 1 mM GSH 时，这些改变明显得到预防，而 GSH 的上述作用被 Akt 抑制剂阻断。
结论
GSH 可能通过激活 Akt 通路来预防 FFAs 诱导的 HBVEC 损伤、氧化应激和凋亡。
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