HO-1通过下调ACAT-1表达抑制小鼠平滑肌源性泡沫细胞形成的机制  

Mechanism of HO-1 inhibiting VSMC foam cell formation by down-regulating ACAT-1 expression

作　　者：康周城 张光运 尹延伟 KANG Zhou-Cheng;ZHANG Guang-Yun;YIN Yan-Wei(Department of Neurology,Xijing Hospital,Air Force Medical University,Xi′an 710032,Shaanxi,China)

机构地区：[1]空军军医大学附属西京医院神经内科,陕西西安710032 [2]空军特色医学中心神经内科

出　　处：《中国老年学杂志》2021年第9期1892-1895,共4页Chinese Journal of Gerontology

基　　金：国家自然科学基金项目(81500356);北京市科技新星计划(Z171100001117094)。

摘　　要：目的探讨血红素加氧酶(HO)-1在血管平滑肌细胞(VSMCs)泡沫样变过程中的作用及可能机制。方法采用C57BL/6J背景野生型雄性小鼠主动脉来源VSMCs建立离体细胞模型。分别应用氧化型低密度脂蛋白(ox-LDL)、HO-1激动剂钴原卟啉(CoPPIX)和抑制剂锌卟啉(ZnPPIX)刺激模型细胞;油红O染色观察VSMCs内脂质聚积情况;酶荧光法检测VSMCs胆固醇水平;Western印迹检测胆固醇酰基转移酶(ACAT)-1蛋白表达。结果ox-LDL刺激VSMCs 72 h显著诱导VSMCs泡沫化,胆固醇水平显著增加;CoPPIX+ox-LDL组VSMCs内脂滴聚积较ox-LDL组明显减轻,伴ACAT-1水平显著下调;ZnPPIX+ox-LDL组VSMCs内脂滴聚积较ox-LDL组更明显,伴ACAT-1水平显著上调,差异均有统计学意义(均P<0.05)。结论激活HO-1可通过下调ACAT-1蛋白表达抑制VSMCs源性泡沫细胞的形成。Objective To investigate the role of heme oxygenase(HO)-1 in vascular smooth muscle cells(VSMC)foam cell formation and the possible mechanism.Methods Primary VSMCs isolated from the thoracic aorta of wild-type male mice C57BL/6J were used as cell model in vitro.Model cells were stimulated by oxidized low density lipoprotein(ox-LDL),HO-1 activator cobalt protoporphyrin(CoPPIX)and HO-1 inhibitor zinc protoporphyrin(ZnPPIX),respectively.The lipid deposition in VSMCs was identified with oil red O staining.Enzyme immunoassay was used to detect cholesterol levels in VSMCs.Western blot was used to observe the expression of cholesterol acyltransferase(ACAT)-1 in VSMCs.Results ox-LDL stimulation for 72 h induced VSMC foam cell formation and increased cholesterol levels significantly.Lipid droplets in the VSMCs of CoPPIX+ox-LDL group were significantly decreased compared with that of ox-LDL group,and the process was accompanied by the down-regulation of ACAT-1.However,lipid droplets in the VSMCs of ZnPPIX+ox-LDL group were significantly increased compared with that of ox-LDL group,and this process was significantly accompanied by up-regulation of ACAT-1 level.The differences were all significant(P<0.05).Conclusions The activated HO-1 could inhibit VSMCs foam cell formation by down-regulating ACAT-1 expression.

关 键 词：血红素加氧酶-1 胆固醇酰基转移酶-1 血管平滑肌细胞 泡沫细胞 

分 类 号：R39[医药卫生—基础医学]