Adipophilin在动脉粥样硬化病变和脂质负荷细胞中的作用研究(英文)

Adipophilin是细胞内脂质聚集和与脂质聚集有关疾病的标志物 ,巨噬细胞源性泡沫细胞的形成是动脉粥样硬化性疾病发生的重要环节 .为了探讨adipophilin在动脉粥样硬化性疾病的作用 ,通过高胆固醇饲料喂养新西兰白兔 12周 ,复制动脉粥样硬化疾病模型 ,同时测定血脂的变化和动脉壁胆固醇 ,使用HE染色、苏丹Ⅳ染色观察动脉粥样硬化病变的形成 ,使用免疫组织化学的方法观察动脉粥样硬化病变处和动物肝脏中adipophilin的表达 .结果发现 ,高胆固醇饲料喂养组血清总胆固醇、低密度脂蛋白胆固醇和动脉壁胆固醇明显增高 ,动脉粥样硬化病变面积增加到 (40 0 6± 7 2 9) % ,动脉粥样硬化病变处adipophilin表达呈阳性 ;而adipophilin在肝脏中的表达无论是高胆固醇饲料喂养组或对照组均为阴性 .使用80mg/L OxLDL与小鼠腹膜巨噬细胞共孵育 ,复制脂质负荷细胞 ,然后把构建的 1mmol/Ladipophilin反义寡核苷酸与该细胞共孵育 .结果发现 ,使用油红O染色观察的细胞内脂滴明显减少 ,生化测定细胞内胆固醇酯显著降低 ,与对照组相比 ,差别有显著性 .说明adipophilin与动脉粥样硬化病变有密切的关系 ,控制adipophilin的表达能够减少巨噬细胞细胞内胆固醇酯的聚集

Induced Expression of Adipophilin With High Cholesterol Diet in Rabbit Atherosclerotic Lesions and Reduced Lipid Accumulation with Adipophilin Antisense in Mouse Macrophages

Adipophilin is a specific marker for lipid accumulation in a variety of cells and for diseases associated with fat-accumulating cells. Lipid-laden foam cells derived from macrophages play a critical role in the development of atherosclerosis. By immunohistochemistry with specific monoclonal antibody, it was shown that expression of adipophilin is induced by high-cholesterol-diet feeding in rabbit atherosclerotic lesions. New Zealand white rabbits were fed with high cholesterol chow for 12 weeks. The level of serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, and cholesterol content of aortic wall was investigated. The areas of fatty streak of the aortas was measured after staining with SudanⅣ. The aortic, and liver specimens with HE and immunohistochemistry staining were observed with light microscopes. The level of serum total cholesterol, low density lipoprotein cholesterol, and cholesterol of aortic wall was significantly increased and the areas of fatty streak of the aortas was (40.06±7.29)% at the end of 12-week-cholesterol feeding. The fatty streak of the aorta with immunohistochemistry staining was strongly positive for adipophilin in animals fed with high cholesterol chow, and the liver was negative with or without high cholesterol chow. Antisense oligodeoxynucleotides of mouse adipophilin was also constructed, mouse peritoneum macrophages was cultured with oxLDL or oxLDL plus the antisense fragment. The results showed that adipophilin antisense decreased cellular cholesterol and lipid droplet content of the cell. The data suggested that the expression of adipophilin in vessel walls is related to the hypercholesterolemia, and has a potential role in lipid accumulation in macrophages and pathogenesis of atherosclerosis.