二仙汤对围绝经期大鼠心脏电生理的影响
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摘要
目的:探讨二仙汤对围绝经期大鼠心脏电生理的作用及机制。方法:雌性SD大鼠,根据体质量随机分组,分为假手术组,模型组,戊酸雌二醇组(8×10~(-4)g·kg~(-1)·d~(-1)),二仙汤低、中、高剂量组(4,8,12 g·kg·~(-1)d~(-1))。除假手术组外,其余各组大鼠均彻底摘除卵巢复制围绝经期大鼠模型。同时分别灌胃给药,假手术组和模型组则灌胃等量生理盐水,每天1次,连续80 d。以生物信号采集仪连接Ⅱ导联电极记录大鼠心电图,酶联免疫吸附测定(ELISA)检测大鼠血清中雌二醇(E2)的含量,苏木素-伊红(HE)染色观察大鼠子宫病理形态学变化,蛋白免疫印迹法(Western bot)检测大鼠心肌组织中雌激素α受体(ERα)蛋白的表达。结果:与假手术组比较,模型组大鼠心电图P波,R波,T波幅度显著减小(P <0. 01),PR间期,QRS时程,QT间期不同程度的缩短,大鼠血清中E2水平显著降低(P <0. 01);大鼠子宫明显干瘪,皱缩,子宫内膜层变薄,腺体数量明显减少;心肌组织ERα受体蛋白表达显著降低(P <0. 01)。与模型组比较,二仙汤各剂量组均能改善上述大鼠子宫的病理变化,中、高剂量二仙汤能显著升高E2水平(P <0. 01),显著逆转上述子宫的病理变化,上调ERα受体蛋白的表达(P <0. 01)。结论:二仙汤能改善围绝经期大鼠的心脏电生理变化,其机制可能与提高大鼠体内雌激素活性和雌激素受体表达有关。
Objective: To explore the effect and mechanism of Erxian decoction on peri-menopausal cardiac electrophysiology in rats. Method: Female sprague-dawley rats were randomly divided into six groups:sham operation group,model group,estradiol valerate group,and low,medium and high-dose Erxian decoction groups. Except the sham operation group,the rats in the other groups were completely removed from the ovarian replication peri-menopausal rat model. At the same time,estradiol valerate group( 8 × 10~(-4) g·kg~(-1)·d~(-1)),lowdose Erxian decoction group( 4 g·kg~(-1)·d~(-1)),middle-dose Erxian decoction group( 8 g·kg~(-1)·d~(-1)) and high-dose Erxian decoction group( 12 g·kg~(-1)·d~(-1)),sham operation group and model group were given the same amount of normal saline. The administration was given once a day for 80 consecutive days. The electrocardiogram of rats was recorded by biosignal detector connected to lead Ⅱ electrode. The content of estradiol( E2) in rat serum was detected by enzyme-linked immuno sorbent assay( ELISA). The pathological changes of rat uterus were observed by hematoxylin-eosin. The expression of the estrogen alpha receptor( ERα) protein was detected by Western blot method in myocardial tissue of rat. Result: Compared with the sham operation group,the amplitudes of P wave,R wave and T wave in the electrocardiogram of the model group were significantly decreased( P < 0. 01),and the PR interval,QRS time course and QT interval were shortened to different degrees. The E2 level was significantly lower( P < 0. 01). The uterus was obviously shriveled and shrank,the endometrial layer became thinner,and the number of glands reduced significantly. The expression of ERα receptor protein in myocardial tissue was significantly decreased( P < 0. 01). Compared with the model group,the Erxian decoction group could improve the pathological changes of ECG in the above rats. The medium and high-dose Erxian decoction can significantly increase the E2 level( P < 0. 01),reverse significantly the pathological changes of the uterus,and up-regulate the expression of ERα receptor protein( P < 0. 01). Conclusion: Erxian decoction can improve cardiac electrophysiological changes in peri-menopausal rats,and its mechanism may be related to the increase of estrogen activity and estrogen receptor expression in rats.
Objective: To explore the effect and mechanism of Erxian decoction on peri-menopausal cardiac electrophysiology in rats. Method: Female sprague-dawley rats were randomly divided into six groups:sham operation group,model group,estradiol valerate group,and low,medium and high-dose Erxian decoction groups. Except the sham operation group,the rats in the other groups were completely removed from the ovarian replication peri-menopausal rat model. At the same time,estradiol valerate group( 8 × 10~(-4) g·kg~(-1)·d~(-1)),lowdose Erxian decoction group( 4 g·kg~(-1)·d~(-1)),middle-dose Erxian decoction group( 8 g·kg~(-1)·d~(-1)) and high-dose Erxian decoction group( 12 g·kg~(-1)·d~(-1)),sham operation group and model group were given the same amount of normal saline. The administration was given once a day for 80 consecutive days. The electrocardiogram of rats was recorded by biosignal detector connected to lead Ⅱ electrode. The content of estradiol( E2) in rat serum was detected by enzyme-linked immuno sorbent assay( ELISA). The pathological changes of rat uterus were observed by hematoxylin-eosin. The expression of the estrogen alpha receptor( ERα) protein was detected by Western blot method in myocardial tissue of rat. Result: Compared with the sham operation group,the amplitudes of P wave,R wave and T wave in the electrocardiogram of the model group were significantly decreased( P < 0. 01),and the PR interval,QRS time course and QT interval were shortened to different degrees. The E2 level was significantly lower( P < 0. 01). The uterus was obviously shriveled and shrank,the endometrial layer became thinner,and the number of glands reduced significantly. The expression of ERα receptor protein in myocardial tissue was significantly decreased( P < 0. 01). Compared with the model group,the Erxian decoction group could improve the pathological changes of ECG in the above rats. The medium and high-dose Erxian decoction can significantly increase the E2 level( P < 0. 01),reverse significantly the pathological changes of the uterus,and up-regulate the expression of ERα receptor protein( P < 0. 01). Conclusion: Erxian decoction can improve cardiac electrophysiological changes in peri-menopausal rats,and its mechanism may be related to the increase of estrogen activity and estrogen receptor expression in rats.
引文
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[3]田秀娟,盛敏佳.激素替代治疗对绝经后女性心脑血管疾病的影响[J].中国老年学杂志,2009,29(18):2376-2377.
[4]马艺鑫,程岩岩,冷雪,等.枸杞多糖对去卵巢大鼠心脏结构及心脏功能的影响[J].辽宁中医杂志,2016,43(8):1745-1747.
[5]年华.二仙汤抗骨质疏松的物质基础研究[D].上海:第二军医大学,2006.
[6]康建颖,陆月红.二仙汤治疗围绝经期综合症患者的临床疗效及对性激素的影响[J].健康研究,2017,37(3):321-323.
[7]冒湘琳,鲍伟倩,赵丕文,等.二仙汤对卵巢早衰大鼠卵巢储备功能的影响[J].中华中医药杂志,2017,32(2):771-773.
[8]刘志文,刘波,吴琪,等.二仙汤对去卵巢骨质疏松大鼠股骨蛋白质组的影响[J].中国中药杂志,2017,42(13):2558-2563.
[9]刘波,刘志文,王莹,等.二仙汤改善去卵巢大鼠学习记忆能力的海马蛋白质组学研究[J].中国中药杂志,2018,43(14):2991-2998.
[10]韦静,杨勇莉.围绝经期妇女骨质疏松浅析[J].临床医药文献电子杂志,2018,5(87):195.
[11]徐春芳,王立中.围绝经期女性雌激素水平与骨代谢指标变化的相关性研究[J].中国妇幼保健,2017,32(6):1229-1232.
[12]彭莉,苏泽琦,赵保胜,等.滋阴安神方对实验性更年期模型大鼠的影响[J].中国实验方剂学杂志,2018,24(15):137-142.
[13]董冰峰,方肇勤,施建蓉,等.二仙汤及其拆方对大鼠卵泡颗粒细胞分泌功能的影响[J].中国中西医结合杂志,2006,26(S1):122-125.
[14]陶仕英,牛建昭,杨美娟,等.二仙汤及其组方中药对幼年大鼠卵巢形态学影响[J].中华中医药杂志,2010,25(12):1995-1998.
[15]谢珍,刘波,徐彭,等.二仙汤及其拆方对去卵巢大鼠更年期综合征的影响[J].中国老年学杂志,2015,35(20):5691-5693.
[16]刘波,陈明,李姗姗,等.二仙汤对去卵巢大鼠骨质疏松的影响[J].中国骨质疏松杂志,2014,20(2):129-132.
[17]陈彦静,向丽华,张治国,等.去卵巢对大鼠心肌损伤及二仙汤的保护作用研究[J].中国病理生理杂志,2015,31(10):1897-1898.
[18]赵兰平,陈彦静,薛淑芳,等.二仙汤对去卵巢大鼠心脏电活动的影响[J].中国实验方剂学杂志,2016,22(5):136-140.
[19]田硕,白明,苗明三.杜仲叶总黄酮对围绝经期大鼠模型的影响[J].中华中医药杂志,2018,33(12):5386-5391.
[20]田硕,白明,苗明三.基于围绝经期综合征临床病症特点的动物模型分析[J].中国实验方剂学杂志,2015,21(19):217-221.
[21]樊官伟,苏李娜,郭茂娟.围绝经期综合征实验模型研究进展[J].辽宁中医杂志,2014,41(1):184-186.
[22]许惠娟,李生强,陈娟,等.绝经后骨质疏松症不同年龄段中医证型分布特点[J].中国实验方剂学杂志,2017,23(12):157-161.
[23]王莹,杨硕,谢慧慧,等.二仙汤对去卵巢大鼠认知障碍的影响[J].中国实验方剂学杂志,2018,24(17):114-119.
[24] Mendelsohn M E,Karas R H. Molecular and cellular basis of cardiovascular gender differences[J]. Science,2005,308:1583-1587.
[25] Knowlton A A,Lee R. Estrogen and the cardiovascular system[J], Clin Pharmacol Ther,2012,135(1):54-70.
[26] Fliegner D,Schubert C,Penkalla A,et al. Female sex and estrogen receptor-βattenuate cardiac remodeling and apoptosis in presssure overload[J]. Am J Physiol Regi,2010,298:R1597-R1606.
[27] De Naeyer A,Pocock V,Milligan S,et al. Estrogenic activity of a polyphenolic extract of the leaves of epimedium brevicornum[J]. Fitoterapia,2005,76(1):35-40.
[28] Lagari V S,Levis S. Phytoestrogens and bone health[J]. Diabetes Obes Metab,2010,17(6):546-553.
[29]胡令军.低剂量雌激素替代治疗对围绝经期综合征患者激素水平及生活质量的影响[J].实用妇科内分泌杂志:电子版,2018,5(15):31-32.
[30] Favre J,GAO J,Henry J P,et al. Endothelial estrogen receptor{alpha}plays an essential role in the coronary and myocardial protective effects of estradiol in ischemia/reperfusion[J]. Arterioscl Throm Vas,2010,30:2562-2567.
[31] Mahmoodzadeh S,Fritschka S,Dworatzek E,et al.Nuclear factor-kappaB regulates estrogen receptor-alpha transcription in the human heart[J]. J Biol Chem,2009,284(37):24705-24714.
[2] Iorga A,Cunningham C M,Moazeni S,et al. The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy[J]. Biol Sex Differ,2017,8(1):33.
[3]田秀娟,盛敏佳.激素替代治疗对绝经后女性心脑血管疾病的影响[J].中国老年学杂志,2009,29(18):2376-2377.
[4]马艺鑫,程岩岩,冷雪,等.枸杞多糖对去卵巢大鼠心脏结构及心脏功能的影响[J].辽宁中医杂志,2016,43(8):1745-1747.
[5]年华.二仙汤抗骨质疏松的物质基础研究[D].上海:第二军医大学,2006.
[6]康建颖,陆月红.二仙汤治疗围绝经期综合症患者的临床疗效及对性激素的影响[J].健康研究,2017,37(3):321-323.
[7]冒湘琳,鲍伟倩,赵丕文,等.二仙汤对卵巢早衰大鼠卵巢储备功能的影响[J].中华中医药杂志,2017,32(2):771-773.
[8]刘志文,刘波,吴琪,等.二仙汤对去卵巢骨质疏松大鼠股骨蛋白质组的影响[J].中国中药杂志,2017,42(13):2558-2563.
[9]刘波,刘志文,王莹,等.二仙汤改善去卵巢大鼠学习记忆能力的海马蛋白质组学研究[J].中国中药杂志,2018,43(14):2991-2998.
[10]韦静,杨勇莉.围绝经期妇女骨质疏松浅析[J].临床医药文献电子杂志,2018,5(87):195.
[11]徐春芳,王立中.围绝经期女性雌激素水平与骨代谢指标变化的相关性研究[J].中国妇幼保健,2017,32(6):1229-1232.
[12]彭莉,苏泽琦,赵保胜,等.滋阴安神方对实验性更年期模型大鼠的影响[J].中国实验方剂学杂志,2018,24(15):137-142.
[13]董冰峰,方肇勤,施建蓉,等.二仙汤及其拆方对大鼠卵泡颗粒细胞分泌功能的影响[J].中国中西医结合杂志,2006,26(S1):122-125.
[14]陶仕英,牛建昭,杨美娟,等.二仙汤及其组方中药对幼年大鼠卵巢形态学影响[J].中华中医药杂志,2010,25(12):1995-1998.
[15]谢珍,刘波,徐彭,等.二仙汤及其拆方对去卵巢大鼠更年期综合征的影响[J].中国老年学杂志,2015,35(20):5691-5693.
[16]刘波,陈明,李姗姗,等.二仙汤对去卵巢大鼠骨质疏松的影响[J].中国骨质疏松杂志,2014,20(2):129-132.
[17]陈彦静,向丽华,张治国,等.去卵巢对大鼠心肌损伤及二仙汤的保护作用研究[J].中国病理生理杂志,2015,31(10):1897-1898.
[18]赵兰平,陈彦静,薛淑芳,等.二仙汤对去卵巢大鼠心脏电活动的影响[J].中国实验方剂学杂志,2016,22(5):136-140.
[19]田硕,白明,苗明三.杜仲叶总黄酮对围绝经期大鼠模型的影响[J].中华中医药杂志,2018,33(12):5386-5391.
[20]田硕,白明,苗明三.基于围绝经期综合征临床病症特点的动物模型分析[J].中国实验方剂学杂志,2015,21(19):217-221.
[21]樊官伟,苏李娜,郭茂娟.围绝经期综合征实验模型研究进展[J].辽宁中医杂志,2014,41(1):184-186.
[22]许惠娟,李生强,陈娟,等.绝经后骨质疏松症不同年龄段中医证型分布特点[J].中国实验方剂学杂志,2017,23(12):157-161.
[23]王莹,杨硕,谢慧慧,等.二仙汤对去卵巢大鼠认知障碍的影响[J].中国实验方剂学杂志,2018,24(17):114-119.
[24] Mendelsohn M E,Karas R H. Molecular and cellular basis of cardiovascular gender differences[J]. Science,2005,308:1583-1587.
[25] Knowlton A A,Lee R. Estrogen and the cardiovascular system[J], Clin Pharmacol Ther,2012,135(1):54-70.
[26] Fliegner D,Schubert C,Penkalla A,et al. Female sex and estrogen receptor-βattenuate cardiac remodeling and apoptosis in presssure overload[J]. Am J Physiol Regi,2010,298:R1597-R1606.
[27] De Naeyer A,Pocock V,Milligan S,et al. Estrogenic activity of a polyphenolic extract of the leaves of epimedium brevicornum[J]. Fitoterapia,2005,76(1):35-40.
[28] Lagari V S,Levis S. Phytoestrogens and bone health[J]. Diabetes Obes Metab,2010,17(6):546-553.
[29]胡令军.低剂量雌激素替代治疗对围绝经期综合征患者激素水平及生活质量的影响[J].实用妇科内分泌杂志:电子版,2018,5(15):31-32.
[30] Favre J,GAO J,Henry J P,et al. Endothelial estrogen receptor{alpha}plays an essential role in the coronary and myocardial protective effects of estradiol in ischemia/reperfusion[J]. Arterioscl Throm Vas,2010,30:2562-2567.
[31] Mahmoodzadeh S,Fritschka S,Dworatzek E,et al.Nuclear factor-kappaB regulates estrogen receptor-alpha transcription in the human heart[J]. J Biol Chem,2009,284(37):24705-24714.