黄芪多糖对Tg诱导PERK/eIF2α通路介导HT29细胞凋亡的保护机制研究  

Protective Mechanism of Astragalus Polysaccharide on Thapsigargin-Induced PERK/eIF2αPathway-Mediated Apoptosis of HT29 Cells

作　　者：郑烈 闻新丽 段盛蕾 Zheng Lie;Wen Xinli;Duan Shenlei(Shaanxi Provincial Hospital of Tradi-tional Chinese Medicine,Shaanxi,Xi′an 710003,China.)

机构地区：[1]陕西省中医医院,陕西西安710003

出　　处：《中国中医急症》2022年第2期222-224,246,共4页Journal of Emergency in Traditional Chinese Medicine

基　　金：陕西省自然科学基础研究计划一般项目(2019JM-580),陕西省中医药管理局科研项目(2019-ZZ-JC010);陕西省中医医院院级课题(2018-04)。

摘　　要：目的探讨黄芪多糖对毒胡萝卜素内酯(Tg)诱导PERK/eIF2α通路介导HT29细胞凋亡的保护作用。方法将细胞分为空白组、模型组、黄芪多糖低剂量组、黄芪多糖高剂量组。除空白组外,其余组给予1μmol/L Tg诱导24 h后进行PERK及p-eIF2α蛋白表达的检测。结果用Tg诱导HT29细胞,PERK及p-eIF2α水平随时间延长呈依赖性增加(P<0.05)。与空白组比较,模型组CHOP表达明显增加(P<0.05);与模型组比较,黄芪多糖低、高剂量组CHOP表达均减少(P<0.05)。与空白组比较,模型组PERK、p-eIF2α蛋白质表达明显增加(P<0.01),通过不同剂量黄芪多糖干预后,PERK、p-eIF2α蛋白质表达呈下降趋势(P<0.05)。Tg诱导HT29细胞后明显增加Caspase-3的凋亡(P<0.01),给予不同剂量黄芪多糖干预后HT29细胞Caspase-3的凋亡率较模型组下降(P<0.05或P<0.01),且高剂量黄芪多糖明显优于低剂量组(P<0.05)。结论毒胡萝卜素内酯诱导HT29细胞凋亡可能与激活内质网应激PERK/p-eIF2α信号通路密切相关,黄芪多糖具有干预该信号通路作用,能抑制HT29细胞凋亡。Objective:To investigate the protective effect of astragalus polysaccharides on thapsigargin(Tg)-induced PERK/eIF2αpathway-mediated HT29 cells apoptosis.Methods:The expression of PERK and p-eIF2αprotein in HT29 cells at different time after induction of 1μmol/L Tg was observed.The cells were divided into blank cell group,Thapsigargin model group,Tg+Astragalus polysaccharide(APS)low-dose group,and Tg+APS high-dose group.Except for the control group,the other groups were treated with 1μmol/L Tg for 24 h after induction.Results:In HT29 cells induced by Tg,the levels of PERK and p-eIF2αincreased in a time-dependent manner(P<0.05).Compared with the control group,the expression of CHOP in the Tg group was significantly increased(P<0.05);compared with the Tg group,the expression of CHOP in the APS low-dose group and APS high-dose group decreased(P<0.05).Compared with the control group,the protein expressions of PERK and peIF2αin the Tg group were significantly increased(P<0.01).After the intervention of different concentrations of APS,the protein expressions of PERK and p-e IF2αshowed a downward trend(P<0.05).In the Tg-induced HT29 cells,the apoptosis of Caspase-3 was significantly increased(P<0.01),and the apoptotic rate of Caspase-3 in HT29 cells after treatment with different concentrations of APS was lower than that in the Tg group(P<0.05 or P<0.01),and the APS high-dose group was significantly better than the low-dose group(P<0.05).Conclusion:Tg-induced apoptosis of HT29 cells may be closely related to the activation of endoplasmic reticulum stress PERK/p-eIF2αsignaling pathway.Astragalus polysaccharide can interfere with this signaling pathway and can inhibit the apoptosis of HT29 cells.

关 键 词：HT29细胞 细胞凋亡 黄芪多糖 毒胡萝卜素内酯 PERK/eIF2α通路 内质网应激 

分 类 号：R285.5[医药卫生—中药学]