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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。
In this study, sphingomyelin synthase 2 knockout (SMS2 - / -) mice were used to investigate the relationship between sphingomyelin (SM) metabolism and atherosclerosis (AS) The relationship between the occurrence. The male 3-month-old SMS2 - / - mice were used as the experimental group and the same-sex C57BL / 6J (wild-type, WT) mice as the control group. Both groups of mice were fed a high-fat, high-cholesterol diet and bile salts were given to promote the formation of AS plaque. Three months after feeding, the aortic arch was dissected and the aorta of the thoracoabdominal and abdominal aorta was dissected to observe the occurrence of AS plaque. At the same time, the peritoneal macrophages of mice were collected and stimulated with lipopolysaccharide, Methods The levels of nuclear factor-κB (NFκB) p65 were detected by enzyme-linked immunosorbent assay (ELISA). Serum levels of SM were measured before and after high-fat diet feeding. The results showed that ASM was rarely found in the aortic arch and the thoracoabdominal aorta of SMS2 - / - mice after 3 months of feeding in high fat diet, whereas more AS plaques were produced in WT mice; (P <0.05), while there was no significant difference in serum lipid level between SMS2 - / - mice and WT mice (P> 0.05). After feeding with high fat diet, the levels of SM in SMS2 - / - The NFκBp65 content of macrophages stimulated by lipopolysaccharide was significantly lower than WT mice. These results suggest that the absence of SMS2 gene has anti-AS and anti-inflammatory effects, which may become a new strategy for clinical treatment.