胺碘酮与决奈达隆诱发脂质代谢紊乱的机制研究  

The mechanism of dyslipidemia induced by amiodarone and dronedarone

作　　者：赵圣刚[1] 许建江[1] 孙凤娟 张祥宇[1] 张冉[1] 江力勤[1] ZHAO Shenggang;XU Jianjiang;SUN Fengjuan;ZHANG Xiangyu;ZHANG Ran;JIANG Liqin(The Second Affiliated Hospital of Jiaxing University,Jiaxing 314000,China)

机构地区：[1]嘉兴学院附属第二医院心内科,314000

出　　处：《心电与循环》2020年第5期434-437,共4页Journal of Electrocardiology and Circulation

基　　金：嘉兴市科技局课题(2016AY23056);浙江省自然科学基金(LQ19H020003);浙江省医药卫生科技项目(2019327710)。

摘　　要：目的探讨决奈达隆和胺碘酮诱发血脂代谢紊乱的机制。方法选择SD雄性大鼠30只,随机分为对照组(NC组)、胺碘酮组(AM组)、决奈达隆组(DR组),胺碘酮和决奈达隆药物剂量均为120 mg·kg^-1·d^-1,给药13周,处死大鼠后行肝脏免疫组化测定肝脏甲状腺受体β1(TRβ1)、单磷酸腺苷活化蛋白激酶(AMPK)、过氧化物酶体增殖物激活受体α(PPARα)、低密低脂蛋白受体(LDL-R)表达水平。结果TRβ1多集中于血管周围肝脏细胞上,TRβ1面积分数分别为NC组10.75±2.03,AM组10.64±2.13,DR组10.25±6.63,组间差异无统计学意义(P>0.05)。PPARα面积分数分别为NC组15.22±2.34,AM组13.56±6.72,DR组10.45±7.08;AMPK面积分数分别为NC组26.48±1.23,AM组11.39±6.63,DR组16.06±6.70,组间差异均无统计学意义(均P>0.05)。LDL-R面积分数分别为NC组40.53±6.13,AM组18.70±10.56,DR组26.92±1.84,3组差异有统计学意义(P<0.05),其中NC组高于AM组(P<0.05)。结论胺碘酮可能通过降低LDL-R表达水平来干扰脂质代谢。Objective To explore the mechanism of dyslipidemia induced by dronedarone and amiodarone.Methods Thirty male SD rats were randomly divided into a control group(NC),amiodarone group(AM),and dronedarone group(DR).The doses of amiodarone and dronedarone were both 120 mg·kg^-1·d^-1.13 weeks later the rats were sacrificed for immunohistochemical analysis of liver sections.The thyroid receptorβ1(TRβ1),AMP-activated potein kinase(AMPK),peroxisome proliferator-activated receptorα(PPARα)and low-density lipoprotein receptor(LDL-R)expression were measured.Results TRβ1 was mostly concentrated on liver cells around blood vessels.The area fraction of TRβ1,PPARαand AMPK was 10.75±2.03,15.22±2.34 and 26.48±1.23 in NC group,10.64±2.13,13.56±6.72 and 11.39±6.63 in AM group,10.25±6.63,10.45±7.08 and 16.06±6.70 in DR group,respectively,with no significant difference between groups(all P>0.05).The area fraction of LDL-R was 40.53±6.13 in NC group,18.70±10.56 in AM group and 26.92±1.84 in DR group with significantly difference between NC and AM groups(P<0.05).Conclusion Amiodarone may interfere with lipid metabolism by reducing the expression of LDL-R.

关 键 词：决奈达隆 胺碘酮 脂质代谢紊乱 甲状腺受体 

分 类 号：R541.7[医药卫生—心血管疾病]