17β-雌二醇通过SOCS3抑制泡沫细胞形成的机制初探  

The mechanism of 17β-estradiol (E2) reduces atherosclerosis in ApoE null mice associated with modulating the cholesterol efflux

作　　者：殷艳蓉[1] 袁炜[1] 贺明[1] 田雨灵[1] 乌宇亮[1] 袁祖贻[1] 梁潇[1] YIN Yanrong;YUAN Wei;HE Ming;TIAN Yuling;WU Yuliang;YUAN Zuyi;LIANG Xiao(Department of Cardiology,the First Affiliated Hospital of Xi′an Jiaotong University,Xi′an 710061,China)

机构地区：[1]西安交通大学第一附属医院心血管内科

出　　处：《新疆医科大学学报》2019年第12期1531-1537,共7页Journal of Xinjiang Medical University

基　　金：国家自然科学基金(81800390);陕西省自然科学基础研究计划(2019JM-384);西安交通大学第一附属医院院基金资助项目(2017QN-25)

摘　　要：目的明确雌激素是否能够调节动脉粥样硬化斑块泡沫细胞中的胆固醇流出。方法在体研究通过对5周龄载脂蛋白E(Apolipoprotein E,ApoE)-/-小鼠进行双侧卵巢切除术(OVX,n=16)或假卵巢切除术(Sham组,n=8),将卵巢切除的小鼠分为2组:OVX+E2组(n=8)小鼠皮下注射溶于丙酮的17-β雌二醇(E2)5μg/d,OVX组(n=8)注射丙酮作为对照。观察2组动脉粥样硬化斑块形成、脂质沉积和胆固醇流出情况的差别;体外研究通过干预RAW264.7细胞,观察其胆固醇流出的水平。结果与OVX组相比,Sham组和OVX+E2组血清总胆固醇和甘油三酯水平均下降,差异有统计学意义(P<0.01~0.05)。与OVX组相比,Sham组和OVX+E2组斑块面积分别减少22.03%和21.84%,脂质沉积分别下降20.57%和30.36%(P均<0.01)。E2增加了斑块中ABCA1和SOCS3的表达。在细胞RAW264.7中,E2能够逆转janus激酶/信号转导和转录激活子(JAK/STAT)ABCA1表达的抑制,但这种逆转作用在SOCS3受抑制的细胞中未发现。SOCS3过表达能够通过抑制JAK2/STAT3的磷酸化提高ABCA1的表达。结论E2能够上调巨噬细胞ABCA1的表达,并可通过上调SOCS3进而调控胆固醇流出。ObjectiveTo investigate the effects of 17β-estradiol(E2)on cholesterol efflux in vivo and in vitro.MethodsBilateral ovariectomy(OVX,n=16)or pseudo-ovariectomy(Sham group,n=8)was performed in 5-week-old apolipoproteins E,apo/-mice.Ovariectomy mice were divided into two groups:OVX+E2 group(n=8)was subcutaneously injected with acetone-soluble 17-β-E2(E2)5μg/d,and OVX group(n=8)was injected with acetone as control.The differences were observed of atherosclerotic plaque formation,lipid deposition and cholesterol efflux between the two groups,and the cholesterol efflux levels of RAW264.7 cells were observed by intervention in vitro.ResultsCompared with OVX group,serum total cholesterol and triglyceride levels were shown to be decreased in both Sham group and OVX+E2 group,and the difference was statistically significant(P<0.01).Compared with OVX group,the plaque area of sham group and OVX+E2 group decreased by 22.03%and 21.84%,and lipid deposition decreased by 20.57%and 30.36%,respectively(P<0.01).E2 increases the expression of ABCA1 and SOCS3 in plaques.In cell raw264.7,E2 was able to reverse the inhibition of the expression of janus kinase/signal transduction and transcription activator(JAK/STAT)ABCA1,but this reversal was not found in socs3-suppressed cells.SOCS3 overexpression can enhance ABCA1 expression by inhibiting JAK2/STAT3 phosphorylation.ConclusionE2 reduces atherosclerosis in ApoE null mice associated with up-regulation of ABCA1 expression and modulating the cholesterol efflux,which were dependent on SOCS3 up-regulation.

关 键 词：雌二醇 动脉粥样硬化 ATP结合盒转运蛋白A1 细胞因子信号转导抑制因子3 胆固醇流出 

分 类 号：R543.5[医药卫生—心血管疾病]