内质网应激信号通路在棕榈酸诱导的血管内皮细胞凋亡中的作用  

Role of endoplasmic reticulum stress signaling pathway in high fat-induced cell apoptosis in vascular endothelial cells

作　　者：许文虎[1] 金春子[2] 王晓龙 陈晨 崔兰[1] XU Wen hu;JIN Chun zi;WANG Xiao long;CHEN Chen;CUI Lan(Dept of Cardiovascular Medicine Affiliated Hospital of Yanbain University, Yanji Jilin133000, China;Central Lab Affiliated Hospital of Yanbain University, Yanji Jilin133000, China)

机构地区：[1]延边大学附属医院心血管内科,吉林延吉133000 [2]延边大学附属医院中心实验室,吉林延吉133000

出　　处：《中国药理学通报》2017年第12期1668-1672,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81460039)

摘　　要：目的探讨内质网应激(endoplasmic reticulum stress,ERS)信号通路在棕榈酸诱导的人脐静脉血管内皮细胞(human umbilical vein endothelial cells,HUVECs)凋亡中的作用。方法不同浓度(0.1、0.2、0.4、0.8 mmol·L^(-1))棕榈酸刺激HUVECs(0、12、24、48 h),CCK-8法检测血管内皮细胞增殖能力;免疫印迹法检测血管内皮细胞GRP78、CHOP、PERK、IRE1、ATF6等ERS信号通路蛋白的表达水平;免疫荧光法检测细胞内凋亡水平。结果 0.4 mmol·L^(-1)棕榈酸刺激血管内皮细胞24 h,细胞增殖率明显降低;GRP78、CHOP、PERK、IRE1、ATF6等ERS信号通路蛋白的表达明显升高(P<0.05),细胞凋亡水平明显增高(P<0.05);ERS抑制剂4-苯基丁酸(4-PBA,10 mmol·L^(-1))预处理组血管内皮细胞凋亡水平明显下调(P<0.05)。结论 ERS信号通路在棕榈酸所致血管内皮细胞凋亡的防治中有重要意义。AimTo explore the role of endoplasmic reticulum stress(ERS)signaling pathway in high fat induced cell apoptosis in human umbilical vein endothelial cells(HUVECs).MethodsHUVECs were exposed to different concentrations of palmitic acid(0.1,0.2,0.4,0.8mmol·L-1)for24h and different time points of04mmol·L-1palmitic acid(0,12,24,48h).Cell viability was measured by cell counting kit(CCK8),and the protein expressions of ERS signaling pathway protein such as GRP78,CHOP,PERK,IRE1,ATF6were determined by Western blot.The level of intracellular apoptosis was detected by immunofluorescence.ResultsHUVECs exposed to palmitic acid at04mmol·L-1for24h showed a decrease in their viability and an increase in the expression of ERS signaling pathway proteins(GRP78,CHOP,PERK,IRE1,ATF6)(P<005);cell apoptotic levels significantly increased(P<005).The intracellular apoptosis levels in the vascular endothelial cells of ERS signaling pathway inhibitor4phenylbutyric acid(4PBA,10mmol·L-1)were significantly lower than those of the PA group(P<005).ConclusionActivated ERS signaling pathway might play an important role in the treatment of high fat induced cell apoptosis in vascular endothelial cells.

关 键 词：内质网应激 棕榈酸 血管内皮细胞 4苯基丁酸 人脐静脉血管内皮细胞 凋亡 

分 类 号：R322.2[医药卫生—人体解剖和组织胚胎学] R329.24[医药卫生—基础医学]