JAZF1基因过表达对ApoE^(-/-)小鼠脂代谢及动脉粥样硬化的影响

The effects of JAZF1 gene overexpression on lipids metabolism and atherosclerosis in ApoE^(-/-) mice

目的探讨JAZF1基因过表达对ApoE-/-小鼠脂代谢及动脉粥样硬化(AS)的影响。方法将48只雄性ApoE-/-小鼠随机分为:高脂+空载(GF组)及高脂+JAZF1质粒组(JAZF1组)、高脂+生理盐水组(HF组)。检测各组血脂、生化指标、组织脂质含量、粪便胆汁酸及主动脉内膜粥样硬化病变。采用[1-14 C]醋酸盐腹腔注射,免疫荧光观察JAZF1基因过表达对ApoE-/-小鼠肝脏TC合成代谢及斑块巨噬细胞聚集的影响。结果JAZF1组肝脏JAZF1表达以及HDL-C/TC高于HF、GF组(P均<0.05),而FBG、FIns、TC、胰岛素抵抗指数(HOMA-IR)、动脉粥样硬化指数(AI)、血脂综合指数(LCI)和肝脏TC含量低于HF、GF组(P均<0.05);与HF组和GF组比较,JAZF1组血管内膜脂质堆积减少,主动脉内斑块泡沫细胞聚集较少,斑块面积、斑块面积/管腔面积、主动脉粥样斑块内巨噬细胞CD68表达、肝脏14 C标记TC放射活性及肝和小肠14 C标记TC放射活性降低(P<0.05或P<0.01)。结论 JAZF1基因过表达可减少ApoE-/-小鼠肝脏TC含量,并抑制TC合成,改善脂代谢,抑制巨噬细胞在斑块内的聚集,减轻和延缓AS的形成。

Objective To investigate the effects of JAZF1 gene overexpression on lipid metabolism and atherosclerosis in ApoE-/-mice.Methods Forty-eight male ApoE-/-mice were divided into three groups：high fat diet （HFD） fed ＋ pIRES2-GFP group （GF group）,HFD-fed ＋ pIRES2-JAZF1 group （JAZF1 group）,and HFD-fed ＋ saline water group （HF group）.PIRES2-GF or pIRES2-JAZF1 was injected via tail vein twice a week.Lipid,biochemical indexes,lipid content in tissues,fecal bile acids,and atherosclerotic lesion were detected.The effects of JAZF1 gene overexpression on cholesterol metabolism and plaques macrophage gathered in ApoE-/-mice were estimated by intraperitoneal 14 C-acetate injection and immunofluorescence.Results Hepatic JAZF1 protein expression and HDL-C/TC were significantly higher in JAZF1 group than in HF and GF group （all P〈0.05）.Levels of fasting blood glucose （FBG）,insulin （FIns）,total cholesterol （TC）,HOMA-insulin resistance index （HOMA-IR）,arteriosclerotic index （AI）,lipid comprehensive index （LCI） and liver TC were significantly lower in JAZF1 groups than in HF and GF group （all P〈0.05）.Lipid accumulation in intima,accumulation of foam cells in thoracic aortic plaques,thoracic aortic plaque area,ratios of thoracic aortic plaque area over lumen area,macrophage CD68 in atherosclerotic plaque of aortic root and 14C-labeled cholesterol in both liver and small intestine were markedly reduced （P〈0.05 or P〈0.01） in JAZF1group compared with HF and GF groups.Conclusion JAZF1 gene over-expression can improve atherosclerotic lesion by reducing cholesterol syntheses and inhibiting macrophages accumulation in atherosclerotic plaques.and inhibiting macrophage accumulation in atherosclerotic plaques.