阿托伐他汀对血脂异常兔血清和脂肪细胞分泌肿瘤坏死因子-α的影响

The influences of atorvastatin on levels of tumor necrosis factor-alpha in serum and secreted by adipocytes in hypercholesterolemic rabbits

目的观察阿托伐他汀干预对血脂异常兔血清及脂肪细胞分泌肿瘤坏死因子-α(TNF-α)的影响,并探讨其可能机制。方法10只新西兰大白兔给予高胆固醇饮食饲养8周后,随机分为高胆固醇组和阿托伐他汀组,每组5只。另选普通饮食12周兔5只作为对照组。12周末,取腹股沟皮下脂肪组织行脂肪细胞培养,酶联免疫吸附法检测血清及脂肪细胞培养液中TNF-α水平。半定量逆转录聚合酶链反应测定脂肪细胞TNF-αmRNA的表达。结果阿托伐他汀干预4周能明显降低血脂异常兔血清总胆固醇、低密度脂蛋白胆固醇、TNF-α水平和脂肪细胞TNF-αmRNA表达量(P<0.05)。阿托伐他汀呈剂量依赖性降低脂肪细胞TNF-α表达和分泌。结论阿托伐他汀降低血脂异常兔血清TNF-α水平,其机制可能与其调脂及抑制脂肪细胞TNF-α的分泌有关。

Objective To evaluate the effect of atorvastatin on serum TNF-α concentration and TNF-α secretion of adipocytes in hypereholesterolemic rabbits. Methods Ten male New Zealand white rabbits were fed with high-cholesterol diet for 8 weeks, and were randomly divided into high cholesterol group and atorvastatin group, the control group was fed with normal diet for 12 weeks. Subcutaneous adipose tissue was collected for adipocyte culture. TNF-α concentrations in serum and adipocyte culture supematant were measured by ELISA. TNF-α mRNA expression in adipocytes was evaluated by semi-quantitative reverse transcription-polymerase chain reaction. Results Atorvastatin intervention significantly decreased serum total cholesterol, low density lipoprotein cholesterol, TNF-α levels and TNF-α expression in adipocytes in atorvastatin group compared with high cholesterol group （ P 〈 0.05）. Additionally, atorvastatin inhibited the TNF-α expression and TNF-α secretion in adipocytes in dose-dependent manner（ P 〈 0.05）. Conclusions The results indicated that atorvastatin reduced the serum TNF-α levels in hypereholesterolemic rabbits, which may be related to its hypolipidemic effect and inhibiting effect on TNF-α secretion in adipocytes.