大蒜素通过抑制caspase-12减轻巨噬源性泡沫细胞凋亡

发布时间：2018-04-10 10:18

选题：大蒜素　视角：半胱天冬酶-　引自：《中国病理生理杂志》2017年11期

【摘要】：目的:研究大蒜素对巨噬源性泡沫细胞凋亡和内质网应激(endoplasmic reticulum stress,ERS)凋亡通路关键分子半胱天冬酶-12(caspase-12)的影响,并探讨可能的分子机制。方法:体外培养RAW264.7巨噬细胞,分别给予大蒜素(12.5、25和50 mg/L)和4-苯丁酸(4-phenylbutyric acid,PBA;4 mmol/L)预处理1 h后,加入氧化低密度脂蛋白(oxidized low-density lipoprotein,ox-LDL;100 mg/L)或衣霉素(tunicamycin,TM;4 mg/L)处理24 h。分别采用MTT法和Annexin V-FITC/PI双染法检测细胞活力和凋亡情况;采用相应的试剂盒测定细胞内caspase-3和培养液中乳酸脱氢酶(lactic dehydrogenase,LDH)的活性;采用Western blot技术检测caspase-12的表达变化;油红O染色检测细胞内脂质蓄积;酶比色法测定细胞内总胆固醇含量。结果:与ERS抑制剂PBA相似,大蒜素可减轻oxLDL所致的巨噬细胞损伤,表现为细胞活力增加、LDH漏出减少、细胞凋亡率和caspase-3活性降低(P0.05);ERS诱导剂TM可导致巨噬细胞活力下降,LDH漏出增多及细胞凋亡率升高(P0.05),大蒜素可明显阻断TM的上述作用;大蒜素明显抑制ox-LDL所致的caspase-12活化(P0.05);与TM组相比,大蒜素也可显著抑制TM所诱导的caspase-12活化(P0.05)。另外,大蒜素还可显著抑制ox-LDL所诱导的巨噬细胞内脂质蓄积和泡沫细胞形成(P0.05)。结论:大蒜素可减少ox-LDL所致的巨噬源性泡沫细胞凋亡,其机制可能与抑制caspase-12活化有关。
[Abstract]:Aim: to investigate the effects of allicin on apoptosis of macrophage derived foam cells and endoplasmic reticulum stress (ER) apoptosis pathway in vitro.The cell viability and apoptosis were detected by MTT assay and Annexin V-FITC/PI double staining method, the activity of lactic dehydrogenase lactic dehydrogenase (LDHs) in cell and culture medium was detected by corresponding kit, the expression of caspase-12 was detected by Western blot technique.Lipid accumulation was detected by oil red O staining and total cholesterol content was determined by enzyme colorimetry.Results: similar to that of ERS inhibitor PBA, allicin could attenuate macrophage injury induced by oxLDL.Apoptosis rate and caspase-3 activity decreased (P 0.05) induced by caspase-3 inducer TM could induce the decrease of macrophage viability and increase of cell apoptosis. Allicin could significantly block the above effects of TM, allicin significantly inhibited the caspase-12 activation induced by ox-LDL (P0.05), and compared with TM group, the activity of caspase-12 was significantly inhibited by allicin, and compared with that of TM group, the effect of allicin on the activity of caspase-12 was significantly inhibited, compared with that of TM group.Allicin also significantly inhibited caspase-12 activation induced by TM (P 0.05).In addition, allicin significantly inhibited lipid accumulation and foam cell formation in macrophages induced by ox-LDL.Conclusion: allicin can reduce the apoptosis of macrophage foam cells induced by ox-LDL, and its mechanism may be related to the inhibition of caspase-12 activation.
【作者单位】：泰山医学院动脉粥样硬化研究所;承德医学院附属医院;泰山医学院人口与计划生育学院;泰山医学院口腔医学院;泰山医学院生命科学学院;泰山医学院基础医学院;
【基金】：国家自然科学基金资助项目(No.81570410;No.81370381) 泰山医学院国家级大学生创新训练项目(No.201510439099;No.201510439126) 山东省医药卫生科技发展计划(No.2013WS0319)
【分类号】：R543.5

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