罗格列酮抑制糖基化终产物诱导大鼠血管平滑肌细胞钙化机制

目的探讨罗格列酮抑制糖基化终产物(AGEs)诱导大鼠血管平滑肌细胞(VSMCs)钙化的可能机制。方法在含10 mmol·L~(-1)β-甘油磷酸培养液中加入200 mg·L~(-1)的AGEs及不同浓度(10~(-7)～10~(-5)mol·L~(-1))的罗格列酮体外培养VSMCs,采用甲-酚酞络合酮方法测定细胞钙含量,real time-PCR检测肿瘤坏死因子α(Tnf-α)、白细胞介素6(Il-6)及糖基化终产物受体(Rage)mRNA表达,Western blotting检测Rage蛋白表达,ELISA法检测细胞上清Tnf-α、Il-6水平。结果 AGEs可使VSMCs钙含量增加,Tnf-α、Il-6及Rage mRNA和蛋白表达增加(P<0.01);罗格列酮组均可降低VSMCs细胞层钙含量,抑制上述影响(P<0.05)。结论罗格列酮可能通过抑制VSMCs Rage表达,降低Tnf-α、Il-6表达和分泌,减轻AGEs诱导的VSMCs钙化。

Mechanism of rosiglitazone on advanced glycation end products induced calcification in rat vascular smooth muscle cells

AIM To investigate the mechanism of rosiglitazone on calcification in cultured rat vascular smooth muscle cells(VSMCs) by advanced glycation end products(AGEs).METHODS VSMCs were incubated with DMEM containing 10 mmol·L~(-1) 3-glvcerophosphate and 200 mg·L~(-1) AGEs with or without 10~(-7) - 10~(-5) mol·L~(-1) rosiglitazone.Calcium deposition,the mRNA and protein expression of Tnf-α,Il-6 and Rage were determined by real time-PCR and Western blotting.RESULTS Compared with AGEs treatment alone,addition of rosiglitazone decreased calcium deposition in VSMCs at 72 h.Rosiglitazone also down-regulated AGEs-induced Rage mRNA and protein expression by about 50%at 24 h.In addition,rosiglitazone decreased both mRNA and protein expression of Tnf-α,Il-6 in VSMCs induced by AGEs at 24 h.CONCLUSION Rage contributes at least partially to the AGEs-induced calcification.Rosiglitazone might exert anticalcification effects via blockade of AGE-Rage interaction.