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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
引用本文:任晓妹,任利群,邵华,魏芹,刘乃丰. 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[J]. 中国新药与临床杂志, 2011, 0(4)
作者姓名:任晓妹  任利群  邵华  魏芹  刘乃丰
作者单位:东南大学附属中大医院心内科;东南大学附属中大医院药剂科;东南大学心血管研究所;
基金项目:国家自然科学基金(30840042)
摘    要: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。

关 键 词:糖基化终产物,高级  肌细胞,平滑肌  钙质沉着症  罗格列酮

Mechanism of rosiglitazone on advanced glycation end products induced calcification in rat vascular smooth muscle cells
REN Xiao-mei,REN Li-qun,SHAO Hua,WEI Qin,LIU Nai-feng. Mechanism of rosiglitazone on advanced glycation end products induced calcification in rat vascular smooth muscle cells[J]. Chinese Journal of New Drugs and Clinical Remedies, 2011, 0(4)
Authors:REN Xiao-mei  REN Li-qun  SHAO Hua  WEI Qin  LIU Nai-feng
Affiliation:REN Xiao-mei~(1a),REN Li-qun~(1a),SHAO Hua~(1b),WEI Qin~2,LIU Nai-feng~(1a,2) (1.a.Department of Cardiology,b.Department of Clinical Pharmacology,Zhongda Hospital,Southeast University,Nanjing JIANGSU 210009,China,2.Institute for Cardiovascular Medicine,China)
Abstract: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.
Keywords:glycosylation end products  advanced  myocytes  smooth muscle  calcinosis  rosiglitazone  
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