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胆碱纠正三氧化二砷诱导豚鼠心电图QT间期延长的分子生物学机制
  • ISSN号:2095-4255
  • 期刊名称:《中华地方病学杂志》
  • 时间:0
  • 分类:R540.41[医药卫生—心血管疾病;医药卫生—临床医学;医药卫生—内科学] R373.21[医药卫生—病原生物学;医药卫生—基础医学]
  • 作者机构:[1]哈尔滨医科大学大庆校区药理教研室,163319, [2]哈尔滨医科大学药学院药理教研室,163319, [3]第五临床医学院骨外科,哈尔滨150081
  • 相关基金:国家自然科学基金重点项目(30430780)
中文摘要:

目的观察胆碱对三氧化二砷(arsenic trioxide,As2O3)诱导豚鼠心电图QT间期延长的纠正作用,探讨其分子生物学机制。方法40只豚鼠按体质量随机分为5组:0(对照)、0.4、0.8、1.6mg/kg As2O3组和胆碱+As2O3组(8mg/kg胆碱+1.6mg/kg As2O3),每组8只,静脉给药后,分别测量6个时间点(0、10、30、60、90、120min)的心电图,观察校正的QT间期(QTc)的变化。6h后,提取心肌组织总RNA,用反转录聚合酶链式反应(RT—PCR)方法观察胆碱对As2O3诱导豚鼠心肌L-型钙通道αIC和钾通道GPERG mRNA表达改变的影响。结果在0.8mg/kg As2O3组,60、90、120min时的QTc(354±22、366±31、368±29)与同时间对照组(325±26、336±26、324±20)比较,差异均有统计学意义(P〈0.05或〈0.01);90、120min时的QTc与0min时(334±12)比较,差异均有统计学意义(P〈0.05)。在1.6mg/kg As2O3组,10、30、60、90、120min时的QTc(362±33、380±21、382±35、388±39、388±31)与同时间对照组(328±20、324±25、325±26、336±26、324±20)比较,差异均有统计学意义(P〈0.05或〈0.01);与0min时(329±31)比较,差异均有统计学意义(P〈0.05或〈0.01)。在30、60、90、120min时,胆碱+As2O3组的QTc(337±17、341±15、344±22、343±19)与1.6mg/kg As2O3组相同时间比较,差异均有统计学意义(P〈0.05或〈0.01)。RT—PCR结果显示1.6mg/kg As2O3组的心肌L-型钙通道αIC mRNA表达量为(1.27±0.14),对照组为(1.02±0.12),组间差异有统计学意义(P〈0.01);胆碱+As2O3组的心肌L-型钙通道αIC mRNA表达量为(1.10±0.13),与1.6mg/kg As2O3组比较,差异有统计学意义(P〈0.05)。0-4、0.8、1.6mg/kg As2O3组豚鼠心肌钾通道GPERG mRNA表达量分别为1.29±0.11、1.22±0.12、1.27±0.16,与对照组(1.23±0.08)相比较,差异?

英文摘要:

Objective To observe the therapeutic action of choline on As2O3 induced electrocardiogram (ECG) QT interval prolongation and to further explore molecular biological mechanisms. Methods 40 guinea pigs were divided into 5 groups randomly with 8 rats in each group: control group intravenously injected with saline, experimental group with 0.4, 0.8, 1.6 mg/kg of choline and As2O3 group with 8 mg/kg choline plus 1.6 mg/kg As2O3. After a series of concentration of As2O3 was intravenously given, ECG was monitored at different time(0,10, 30,60,90,120 min), and corrected QT interval(QTc)was studied. Total RNA was abstracted from the guinea pigs hearts after 6 h, and the effects of choline on altered L-type calcium channel αIC and potassium channel GPERG mRNA expression caused by As2O3 in cardiomyocytes of guinea pig were studied by the method of reverse transcription polymerase chain reaction(RT-PCR). Results In 0.8 mg/kg As2O3 group, the value of QTc at 60,90 and 120 min respectively being 354 ± 22,366 ± 31 and 368 ± 29 was significantly higher than that of control groups[ (325 ± 26,336 ± 26 and 324 ± 20) at same time] with a significant difference (P 〈 0.05 or 〈 0.01); the value of QTc at 90 and 120 min was significantly higher than that of 0 min group(334 ± 12), the difference being statistically significant(P 〈 0.05). In 1.6 mg/kg As2O3 group, the value of QTe at 10,30,60,90 and 120 min respectively being 362 ± 33,380 ± 21,382 ± 35,388 ± 39 and 388 ± 31 was significantly higher than that of control groups[ (328 ± 20,324 ± 25,325 ± 26,336 ± 26 and 324 ± 20) at same time] with a significant difference (P 〈 0.05 or 〈 0.01); the value of QTe at 10,30,60,90 and 120 min was significantly higher than that of 0 min group(329 ± 31 ), the difference being statistically significant (P 〈 0.05). In choline + As2O3 group, the value of QTe at 30,60,90 and 120 min was 337 ± 17,341 ± 15,344 ± 22 and 343 ± 19, significantly lower than that of 1.6 mg/k

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期刊信息
  • 《中华地方病学杂志》
  • 中国科技核心期刊
  • 主管单位:中华人民共和国卫生部
  • 主办单位:中华医学会 哈尔滨医科大学
  • 主编:
  • 地址:哈尔滨市南岗区保健路157号
  • 邮编:150081
  • 邮箱:cje2005@163.com
  • 电话:0451-86675924
  • 国际标准刊号:ISSN:2095-4255
  • 国内统一刊号:ISSN:23-1583/R
  • 邮发代号:14-30
  • 获奖情况:
  • 2000年获黑龙江优秀科技期刊奖
  • 国内外数据库收录:
  • 美国化学文摘(网络版),英国农业与生物科学研究中心文摘,波兰哥白尼索引,荷兰文摘与引文数据库,荷兰医学文摘,美国剑桥科学文摘,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版)
  • 被引量:1230