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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 observe the inhibitory effect of rosiglitazone on the activity of rat transmembrane activator of transcription 1 (AP-1) and the expression of transforming growth factor β 1 (TGF-β 1) in high glucose medium, and to investigate the effect of rosiglitazone on Direct protection of the kidneys and related mechanisms. Methods: Rat mesangial cells were divided into control group (C group, normal MEM medium containing 5.6 mmol·L -1 glucose), high glucose group (H group, 30 mmol·L -1) High-glucose MEM medium), mannitol group (M group, 24.2 mmol·L -1 mannitol + C group), high dose rosiglitazone intervention group (RH group, H group +20 μmol·L ~ -1) rosiglitazone, low dose rosiglitazone intervention group (RL group, H group +10 μmol·L -1 rosiglitazone), N-acetylcysteine NAC-antioxidant) intervention group (N group, H group +5 mmol·L -1 NAC). After 48 h, the activity of AP-1 was detected by EMSA. The mRNA and protein levels of TGF-β 1 were detected by RT-PCR and ELISA. Results: The expression of AP-1 and TGF-β 1 in control group and mannitol group had no significant difference. The activity of AP-1 and the level of TGF-β 1 mRNA and protein in high glucose group were significantly higher than those in control group. NAC and rosiglitazone (20μmol·L -1) intervention, the expression of both were significantly lower than the high glucose group. CONCLUSION: Rosiglitazone can reduce the expression of TGF-β 1 induced by high glucose by inhibiting the activity of AP-1, which may be one of the mechanisms by which rosiglitazone can play an immediate renal protective effect.