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  

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

作　　者：谢湘竹[1] 赵水平[2] 于碧莲[2] 钟巧青[2] 

机构地区：[1]解放军总医院南楼心血管一科,北京100853 [2]中南大学湘雅二医院心内科,长沙410011

出　　处：《解放军医药杂志》2012年第5期4-7,共4页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：国家自然科学基金项目(30470705)

摘　　要：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-γmRNA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-αmRNA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-αmRNA表达和NF-κB活化,并增强PPAR-γmRNA表达。1.0及10.0μM阿托伐他汀干预组TNF-α水平、TNF-αmRNA表达低于oxLDL刺激组(P<0.05),10.0μM阿托伐他汀干预组PPAR-γmRNA表达高于oxLDL组,NF-κB活性低于oxLDL刺激组(P<0.05);TNF-α水平、TNF-αmRNA表达、NF-κB活性和PPAR-γmRNA表达10.0和0.1μM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ox-LDL刺激下3T3-L1脂肪细胞TNF-α分泌、TNF-αmRNA表达和NF-κB活性,增强PPAR-γmRNA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。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.

关 键 词：脂细胞 脂蛋白类 LDL 阿托伐他汀 肿瘤坏死因子α 核因子-κB 过氧化物酶体增殖物激活受体 

分 类 号：R972.6[医药卫生—药品] R977.6[医药卫生—药学]