中文摘要：

本文以神经鞘磷脂合成酶2基因敲除（sphingomyelin synthase 2 knockout,SMS2-/-）小鼠为研究对象,旨在探讨神经鞘磷脂（sphingomyelin,SM）代谢与动脉粥样硬化（atherosclerosis,AS）发生之间的关系。雄性3月龄SMS2-/-小鼠为实验组,同性别同月龄C57BL/6J（wild-type,WT）小鼠为对照组。用高脂高胆固醇饮食喂养两组小鼠,并给予胆盐以促进AS斑块的形成。喂养3个月后解剖观察小鼠主动脉弓,剖开胸腹主动脉进行油红染色以观察AS斑块发生情况;同时收集小鼠腹腔巨噬细胞,用脂多糖刺激后,提取核蛋白用Western blot方法检测核因子κB（nuclear factor-κB,NFκB）p65含量;高脂饮食喂养前后,小鼠断尾取血,酶法测定血清SM水平,用血脂检测试剂盒检测血脂水平。结果显示,高脂饮食喂养3个月后,SMS2-/-小鼠的主动脉弓和胸腹主动脉很少形成AS斑块,而WT小鼠则产生了较多AS斑块;高脂饮食喂养前后,SMS2-/-小鼠血清SM水平均明显低于WT小鼠（P〈0.05）,而血脂水平并无显著性差异（P〉0.05）;高脂饮食喂养后,SMS2-/-小鼠腹腔巨噬细胞经过脂多糖刺激产生的NFκBp65含量明显低于WT小鼠。以上结果提示,SMS2基因的缺失有抗AS及抗炎作用,因而可能成为临床治疗的新策略。

英文摘要：

Plasma sphingomyelin（SM） has been shown to be an independent risk factor for coronary heart disease,and sphingomyelin synthase 2（SMS2） contributes to de novo SM biosynthesis and plasma membrane SM levels.The aim of the present study is to evaluate the in vivo role of SMS2 deficiency in serum SM metabolism and atherosclerosis（AS） development.We used male SMS2 knockout（SMS2-/-） and C57BL/6J（wild-type,WT） mice as experimental and control groups,respectively.Each group was fed high-fat diet（1% cholesterol,20% leaf fat）,as well as bile salt for accelerating the atherosclerotic formation.After three months of feeding,the mice were killed to observe aortic arches and oil red-stained longitudinal sections of thoracoabdominal aortae.Fasting blood samples were taken from the tail vein before and after high-fat diet,and the serum lipid and SM levels were measured by using kits and enzymatic method respectively.Western blot was used to analyze the contents of nuclear factor-κB（NFκB） p65 subunit in peritoneal macrophages stimulated with lipopolysaccharide（LPS） after high-fat diet.The results showed that after high-fat diet,SMS2-/-mice presented decreased atherosclerotic lesions in aortic arch and thoracoabdominal aorta compared with WT mice.Regardless of whether high-fat diet were given or not,SMS2-/-mice showed a significant decrease in serum SM level（P0.05）,but no significant changes in serum lipid levels,compared with WT mice.The expressions of NFκB p65 were attenuated in macrophages from SMS2-/-mice in response to LPS stimulation compared with those of the WT mice.These results suggest that SMS2 deficiency decreases AS and inhibits inflammation in mice.Thus,SMS2 deficiency may be a potential therapeutic strategy.