阿托伐他汀对氧化型低密度脂蛋白刺激下脂肪细胞分泌功能的影响

目的 观察阿托伐他汀对氧化型低密度脂蛋白(oxLDL)刺激下3T3-L1脂肪细胞分泌功能的影响,并探讨其作用机制.方法 3T3-L1脂肪细胞促分化成熟后,oxLDL刺激脂肪细胞,给予不同浓度的阿托伐他汀干预,收集细胞,测定脂肪细胞肿瘤坏死因子-α(TNF-α)浓度、TNF-α和PPAR-γ mRNA表达水平及核因子-κB(NF-κB)活性.结果 oxLDL刺激使3T3-L1脂肪细胞分泌TNF-α、TNF-α mRNA表达水平明显增高.阿托伐他汀呈浓度依赖性抑制oxLDL刺激下TNF-α分泌、TNF-α mRNA表达和NF-κB活化,并增强PPAR-γ mRNA表达.1.0及10.0 μM阿托伐他汀干预组TNF-α水平、TNF-α mRNA表达低于oxLDL刺激组(P＜0 05),10.0 μM阿托伐他汀干预组PPAR-γ mRNA表达高于oxLDL组,NF-κB活性低于oxLDL刺激组(P＜0 05);TNF-α水平、TNF-α mRNA表达、NF-κB活性和PPAR-γ mRNA表达10.0和0.1 μM阿托伐他汀干预组比较差异均有统计学意义(P＜0 05).结论 阿托伐他汀能抑制oxLDL刺激下3T3-L1脂肪细胞TNF-α分泌、TNF-α mRNA表达和NF-κB活性,增强PPAR-γ mRNA表达,PPAR-γ与NF-κB可能介导了他汀类药物对脂肪细胞炎性过程的调节.

Effect of Atorvastatin on the Secretion of 3T3-L1 Adipocytes Induced by oxLDL

Objective To evaluate the effect of Atorvastatin on the secretion of 3T3-L1 adipocytes induced by oxLDL and discuss its mechanism. Methods Fully differentiated 3T3-L1 adipoeytes were incubated in the medium containing various Atorvastatin concentrations with oxLDL stimulation. TNF-α levels in supernataut, TNF-α mRNA, PPAR-γ mRNA expression and NF-κB activity were evaluated. Results oxLDL stimulation induced a significant increase of TNF-α secretion and mRNA expression in 3T3-L1 adipocytes. Atorvastatin inhibited TNF-（x secretion, TNF-α mRNA expression and NF-κB activation, and enhanced PPAR-γ mRNA expression in a dose dependent manner. TNF-α secretion and TNF-α mRNA expression in the group treated with atorvastatin at 1.0 and 10.0μM were significantly lower than those in the oxLDL stimulated group （P 〈 0. 05 ）. The PPAR-γ mRNA expression in the group treated with atorvastatin at 10.0 μM were significantly higher than that in the oxLDL stimulated group, while NF-κB activity was significantly lower than that in the oxLDL stimulated group（P 〈0. 05）. TNF-α levels, TNF-α mRNA expression, NF-κB activity and the PPAR-γ mRNA expression were compared between treatment groups with Atorvastatin at 10.0 and 0.1 μM, respectively; the differences were significantly（P 〈 0.05）. Conclusion Atorvastatin can suppress TNF-α secretion, TNF-α mRNA expression and NF-κB activity in oxLDL-stimulated 3T3-L1 adipocytes, and on the other hand, enhance the expression of PPAR-γ mRNA. NF-κB and PPAR-γ signaling pathways may be invlolved in the inflammation in adipocytes.