罗格列酮对高糖环境中大鼠系膜细胞转化生长因子β_1抑制作用的研究  

Inhibitory Effects of Rosiglitazone on the Expression of Transforming Growth Factor-β_1 in Rat Mesangial Cells Cultured in High Glucose

作　　者：包艳[1] 贾汝汉[2] 李竞[1] 孙永林[1] 王颖[1] 

机构地区：[1]武汉大学人民医院内分泌科,武汉430060 [2]武汉大学人民医院肾内科,武汉430060

出　　处：《中国药师》2010年第11期1577-1580,共4页China Pharmacist

摘　　要：目的:观察罗格列酮对高糖培养基中大鼠系膜细胞转录激活蛋白-1(AP-1)活性及转化生长因子β_1(TGF-β_1)表达的抑制作用,探讨罗格列酮对肾脏的直接保护作用及相关机制。方法:将大鼠系膜细胞分为对照组(C组,普通MEM培养基,含5.6 mmol·L^(-1)葡萄糖)、高糖组(H组,30 mmol·L^(-1)高糖MEM培养基)、甘露醇组(M组,24.2 mmol·L^(-1)甘露醇+C组)、大剂量罗格列酮干预组(RH组,H组+20μmol·L^(-1)罗格列酮)、小剂量罗格列酮干预组(RL组,H组+10μmol·L^(-1)罗格列酮);N-乙酰半胱氨酸(N-acetylcysteine,NAC-抗氧化剂)干预组(N组,H组+5 mmol·L^(-1)NAC)。48 h后,采用EMSA检测AP-1的活性,RT-PCR和ELISA法检测TGF-β_1 mRNA及蛋白含量。结果:对照组和甘露醇组AP-1和TGF-β_1的表达无明显差别,高糖组AP-1活性、TGF-β_1 mRNA及蛋白水平较对照组明显升高,采用NAC和罗格列酮(20μmol·L^(-1))干预后,两者表达均较高糖组明显下降。结论:罗格列酮可通过抑制AP-1活性而降低高糖所诱导的TGF-β_1表达,这可能是罗格列酮发挥直接肾脏保护作用的机制之一。Objective： To investigate the inhibitory effects of rosiglitazone on the expression of activating protein-1 （ AP-1 ） and transforming growth factor-β1 （TGF-β1 ） induced by high glucose in rat mesangial cells. Method： The mesangial cells were divided six groups：control group（ C,5. 6 mmol·L-1 glucose）;mannitol group （M,24. 2mmol.L-1 mannitol ＋ group C）;high glucose group （H, 30 mmol. L - 1 glucose） ; RH group （ RH, group H ＋ 20 μmol ·L - 1 rosiglitazone） ; RL group （ RL, group H ＋ 10 μmol · L -1 rosiglitazone） ; N-aeetylcysteine （NAC） group （N,group H ＋5 mmol·L-1 NAC,NAC was added lh before the stimulation of high glucose）. After 48 hours ,the level of AP-1 was measured by EMSA. The mRNA and the protein expression of TGF-β1 were semi-quantitatively determined with reverse transcription-polymerase chain reaction and ELISA respectively. Result： No significant difference of AP-1 and TGF-β1 was found between group C and group M. Comparing with group C, the activity of AP-1, TGF-mRNA and protein in group H was increased markedly, which was prevented by rosiglitazone （20 μmol·L- 1 ） and NAC respectively. Conclusion： Rosiglitazone may suppress high glucose-induced AP-1 activation and TGF-β1 expression,which may be one of the mechanisms that rosiglitazone play a protective role of the kidney

关 键 词：罗格列酮 转化生长因子Β1 转录激活蛋白-1 

分 类 号：R965.1[医药卫生—药理学]