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吡格列酮抑制糖尿病兔心房肌细胞离子通道重构

Pioglitazone inhibits atrial ionic channel remodeling in diabetic rabbits hearts
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摘要 目的 建立四氧嘧啶介导的兔糖尿病(DM)模型,评价吡格列酮对DM兔心房肌细胞离子通道重构的干预作用.方法 本实验在天津心脏病学研究所进行,选取健康成年日本大耳白兔32只随机(随机数字法)分为健康对照组(CN组)、糖尿病组(DM组)、糖尿病+吡格列酮A组[DPG组,4mg/ (d·kg)]和糖尿病+吡格列酮B组[DPI组,8mg/ (d·kg)].通过四氧嘧啶耳缘静脉注射建立兔DM模型,血糖水平≥14 mmol/L认为DM模型建立成功.模型建立成功后饲养8周取出心脏建立Langendorff灌流的离体兔心脏模型分离心房肌细胞,采用全细胞膜片钳技术记录细胞膜动作电位(AP)、L-型钙通道电流(ICa,L)和快钠通道电流(INa),比较各组兔心房肌细胞动作电位时程(APD)和LCa.L、INa电流密度的差别.四组间比较采用单因素方差分析,两两比较采用LSD-t检验.结果 各种刺激频率下DM组APD90和APD∞均明显延长(P<0.05 vs.CN组),APD90频率适应性各组间差异无统计学意义(P >0.05 vs.CN组).DM组ICa.L电流密度增加,INa电流密度减少(P<0.01 vs.CN组).DPG和DPI组APD90和APD50较DM组明显缩短,应用吡格列酮减小ICa.L电流密度且增加INa电流密度,吡格列酮不同给药剂量组间各细胞电生理指标差异无统计学意义.结论 吡格列酮可以抑制DM导致的兔心房离子通道重构. Objective To investigate the effects of pioglitazone on atrial ionic channel remodeling in alloxan-induced diabetic rabbit models.Methods A total of 32 rabbits were randomly (random number) divided into control (CN) group,diabetes mellitus (DM) group,diabetes mellitus + pioglitazone 4 mg/ (d · kg) (DPG) group and diabetes mellitus + double pioglitazone 8 mg/ (d · kg) (DPI) group.The diabetic state was examined by quantitative determination of blood glucose levels of ≥ 14 mmol/L.Langendorff-perfused rabbit hearts were used to isolate single atrial myocyte,and whole-cell patch-clamp technique was used to record action potential duration (APD) and atrial ionic channel currents (ICa,L and INa).Variables with normal distribution were compared with One-way ANOVA and LSD-t test.Results Compared with controls,APD90 and APDS0 of left atrial myocytes were significantly prolonged in DM group (P <0.05 vs.CN),and there was no significant difference in APD90 frequency adaptation between them (P >0.05 vs.CN).The densities of INa were reduced and the densities of ICa,L were increased in DM group (P < 0.01 vs.CN).The above variables were markedly attenuated in DPG and DPI group.Conclusions Pioglitazone may inhibits atrial ionic channel remodeling in diabetic rabbit models.
出处 《中华急诊医学杂志》 CAS CSCD 北大核心 2014年第2期181-186,共6页 Chinese Journal of Emergency Medicine
基金 国家自然科学基金(30900618)
关键词 心房颤动 糖尿病 吡格列酮 膜片钳 动作电位时程 L型钙通道电流 快钠通道电流 离子通道 重构 Atrial fibrillation Diabetes mellitus Pioglitazone Patch-clamp technique Action potential duration L-type calcium channel current Rapid sodium channel current Lonic channel Remodeling
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参考文献18

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