松油烯-4-醇调节棕榈酸诱导胰岛β细胞内质网应激抑制细胞凋亡  

Study on the Effect of Terpine-4-ol on the Regulation of Endoplasmic Reticulum Stress Induced by Palmitic Acid to Inhibit Apoptosis of PancreaticβCells

作　　者：陈虹雨 李金锦 尚雪祎 张闯 张盈 沈祥春[2] 张彦燕[1,2] CHEN Hong-yu;LI Jin-jin;SHANG Xue-yi;ZHANG Chuang;ZHANG Ying;SHEN Xiang-chun;ZHANG Yan-yan(Department of Clinical Pharmacy,College of Pharmacy,Guizhou Medical University,Gui′an New Area 561113,China;Key Laboratory of Optimal Utilization of Natural Medicine Resources,Guizhou Medical University,Gui′an New Area 561113,China)

机构地区：[1]贵州医科大学药学院临床药学教研室,贵州贵安新区561113 [2]贵州医科大学天然药物资源优效利用重点实验室,贵州贵安新区561113

出　　处：《中药材》2024年第4期963-968,共6页Journal of Chinese Medicinal Materials

基　　金：国家自然科学基金资助项目(82060775);贵州医科大学高层次人才启动基金项目(校博合J字[2021]010号);贵州省科技创新基地(黔科合中引地[2023]003)

摘　　要：目的:研究松油烯-4-醇调节棕榈酸诱导的Min6细胞内质网应激,抑制细胞凋亡的作用和机制。方法:分析松油烯-4-醇对棕榈酸诱导Min6细胞内质网应激和细胞凋亡的作用,实验分为正常对照组、模型组、二甲双胍(100μmol/L)组及松油烯-4-醇低(5μmol/L)、高(20μmol/L)浓度组;分析其作用机制,实验分为正常对照组、模型组、内质网应激抑制剂4-苯基丁酸(4-PBA,25 mmol/L)组、松油烯-4-醇(20μmol/L)组、4-PBA(25 mmol/L)+松油烯-4-醇(20μmol/L)组。采用MTT检测细胞活力,流式细胞术检测胞质钙离子含量和细胞凋亡率,Western Blot检测内质网应激标志蛋白p-PERK、ATF4、GRP78和凋亡标志蛋白CHOP、Caspase-3、Caspase-9、Bax的表达水平。结果:与正常对照组比较,模型组细胞胞质钙离子、凋亡率显著升高,细胞活力显著降低,CHOP、Caspase-3、Caspase-9、Bax、ATF4、GRP78蛋白表达及p-PERK/PERK水平显著升高(P<0.01)。与模型组比较,各给药组细胞胞质钙离子、凋亡率显著降低,细胞活力显著升高,CHOP、Caspase-3、Caspase-9、Bax、ATF4、GRP78蛋白表达及p-PERK/PERK水平显著降低(P<0.05或P<0.01)。4-PBA+松油烯-4-醇组与4-PBA组各指标差异无统计学意义(P>0.05)。结论:松油烯-4-醇可通过调节内质网应激抑制棕榈酸诱导下Min6细胞凋亡。Objective:To study the effect and mechanism of terpinen-4-ol on regulation of endoplasmic reticulum stress induced by palmitic acid(PA)and inhibition of cell apoptosis in Min6 cells.Methods:For analyzing the effects of terpine-4-ol on endoplasmic reticulum stress and apoptosis of Min6 cells induced by palmitic acid,the experiments were divided into normal control group,model group,metformin(100μmol/L)group,low(5μmol/L)and high(20μmol/L)concentration of terpine-4-ol groups.For analyzing the mechanism,the experiment was divided into normal control group,model group,endoplasmic reticulum stress inhibitor 4-phenylbutyric acid(4-PBA,25 mmol/L)group,terpine-4-ol(20μmol/L)group,4-PBA(25 mmol/L)with terpine-4-ol(20μmol/L)group.Cell viability was detected by MTT.Cytoplasmic calcium content and apoptosis rate were detected by flow cytometry.The expression levels of endoplasmic reticulum stress markers p-PERK,ATF4,GRP78 and apoptosis markers CHOP,Caspase-3,Caspase-9 and Bax were detected by Western Blot.Results:Compared with normal control group,cytoplasmic calcium ions and apoptosis rate were significantly increased,cell activity was significantly decreased,and protein expressions of CHOP,Caspase-3,Caspase-9,Bax,ATF4,GRP78 and the level of p-PERK/PERK were significantly increased in model group(P<0.01).Compared with model group,cytoplasmic calcium ion and apoptosis rate were significantly decreased,cell activity was significantly increased,protein expressions of CHOP,Caspase-3,Caspase-9,Bax,ATF4,GRP78 and the level of p-PERK/PERK were significantly decreased(P<0.05 or P<0.01).There was no significant difference between 4-PBA with terpine-4-ol group and 4-PBA group(P>0.05).Conclusion:Terpine-4-ol can inhibit palmitic acidinduced apoptosis of Min6 cells by regulating endoplasmic reticulum stress.

关 键 词：松油烯-4-醇 棕榈酸 内质网应激 细胞凋亡 胰岛β细胞 

分 类 号：R285.5[医药卫生—中药学]