附子与山茱萸配伍对慢性心力衰竭大鼠的影响
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摘要
目的探讨附子与山茱萸配伍对慢性心力衰竭大鼠增效减毒作用。方法 ip盐酸阿霉素构建大鼠慢性心力衰竭模型,分别给予附子提取物、山茱萸提取物和附子-山茱萸提取物3周后,检测动物血清脑钠素(BNP)含量,心肌细胞Ca2+-ATP酶和Na~+,K~+-ATP酶活性,镜下观察左心室组织病理学形态变化。结果造模3周后,模型组大鼠普遍出现腹水、消瘦、稀便、弓背等症状体征;左心室射血分数(EF)和左心室短轴缩短率(FS)明显下降;血清BNP水平显著升高;左心室组织出现心肌纤维断裂及心肌细胞变性、坏死等病理改变。连续ig给予附子-山茱萸提取物3周后,大鼠症状及体征明显改善,血清BNP水平下降,心肌细胞Na~+,K~+-ATP酶活性升高,左心室组织病理学形态有明显改善。附子提取物和山茱萸提取物分别连续给药3周,上述指标未见明显改善。结论附子与山茱萸配伍可能通过提高心肌细胞Na~+,K~+-ATP酶活性,改善慢性心力衰竭的心肌能量代谢障碍,提高心力衰竭的心肌活性,起到增效减毒作用。
Objective To study the efficacy enhancing and toxicity reducing effects of compatibility of Aconitum carmichaeli and Cornus officinalis on chronic heart failure(CHF) rats.Methods The CHF rats was established by ip injection of adriamycin(ADM),the CHF rats were administrated tested drugs for three weeks by means of ig administration,the tested drugs included extracts of A.carmichaeli,C.officinalis,and Compound.The serum brain natriuretic peptide(BNP) level,activity of Ca2+-ATP and Na+,K+-ATP enzymes in cardiac myocytes,and cardiac histopathology were measured.Results After three weeks of modeling,the CHF rats showed signs of ascites,loss of weight,loose stool,hogback,etc.The left ventricular ejection fraction(EF) and fraction shortening(FS) decreased significantly,and the level of BNP in serum was significantly improved;Pathological changes of ventricular tissue included rupture of myocardial fibers,degeneration and necrosis of cardiomyocytes,etc.After three weeks of gavage compatibility of A.carmichaeli and C.officinalis,the general state and cardiac histopathology of the animal was obviously improved,the level of BNP in serum was reduced significantly,the activity of Na+,K+-ATP enzymes was increased significantly.No notable improvement in the above indexes was obtained after administration of A.carmichaeli and C.officinalis alone.Conclusion The compatibility of A.carmichaeli and C.officinalis can increase the activity of Na+,K+-ATP enzyme in cardiac myocytes,and improve the energy metabolism and activity of cardiac myocytes in chronic heart failure.The compatibility of A.carmichaeli and C.officinalis play the key role of enhancing efficacy and reducing toxicity.
Objective To study the efficacy enhancing and toxicity reducing effects of compatibility of Aconitum carmichaeli and Cornus officinalis on chronic heart failure(CHF) rats.Methods The CHF rats was established by ip injection of adriamycin(ADM),the CHF rats were administrated tested drugs for three weeks by means of ig administration,the tested drugs included extracts of A.carmichaeli,C.officinalis,and Compound.The serum brain natriuretic peptide(BNP) level,activity of Ca2+-ATP and Na+,K+-ATP enzymes in cardiac myocytes,and cardiac histopathology were measured.Results After three weeks of modeling,the CHF rats showed signs of ascites,loss of weight,loose stool,hogback,etc.The left ventricular ejection fraction(EF) and fraction shortening(FS) decreased significantly,and the level of BNP in serum was significantly improved;Pathological changes of ventricular tissue included rupture of myocardial fibers,degeneration and necrosis of cardiomyocytes,etc.After three weeks of gavage compatibility of A.carmichaeli and C.officinalis,the general state and cardiac histopathology of the animal was obviously improved,the level of BNP in serum was reduced significantly,the activity of Na+,K+-ATP enzymes was increased significantly.No notable improvement in the above indexes was obtained after administration of A.carmichaeli and C.officinalis alone.Conclusion The compatibility of A.carmichaeli and C.officinalis can increase the activity of Na+,K+-ATP enzyme in cardiac myocytes,and improve the energy metabolism and activity of cardiac myocytes in chronic heart failure.The compatibility of A.carmichaeli and C.officinalis play the key role of enhancing efficacy and reducing toxicity.
引文
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[10]Neubauer S.The failing heart-an engine out of fuel[J].N Engl J Med,2007,356(11):1140-1151.
[11]黄丹丹.环维黄杨星D对大鼠心衰的治疗作用及其对心肌Na+-K+-ATPase亚基表达的影响[D].南京:南京中医药大学,2013.
[2]贾雪岩,林华,沈玉巧,等.附子新型炮制品中乌头类生物碱测定及其强心作用研究[J].药物评价研究,2016,39(2):224-229.
[3]卢志强,张艳军,庄朋伟,等.附子对急性心力衰竭大鼠血流动力学影响及其机制研究[J].中草药,2015,46(21):3223-3227.
[4]李庆利,曾贵荣,谭志超,等.参附注射液对大鼠慢性心力衰竭的保护作用研究[J].中南药学,2017,15(12):1717-1721.
[5]汪星,孙卫,张铁军.乌头类有毒中药配伍减毒增效的研究进展[J].中国实验方剂学杂志,2012,18(18):327-331.
[6]舒华.温阳振衰颗粒联合运动训练对慢性心衰大鼠心肌能量代谢的影响[D].长沙:湖南中医药大学,2016.
[7]Singal P K,Li T,Kumar D,et al.Adriamycin-induced heart failure:Mechanism and modulation[J].Mol Cell Biochem,2000,207(12):77-86.
[8]Buja L M,Ferrans V J,Mayer R J,et al.Cardiac ultrastructural changes induced by daunorubicin therapy[J].Cancer,1973,32(4):771-788.
[9]徐建虎,张琦,杨子庆,等.阿霉素诱导大鼠慢性心衰模型的制备[J].宁夏医科大学学报,2016,38(3):348-351.
[10]Neubauer S.The failing heart-an engine out of fuel[J].N Engl J Med,2007,356(11):1140-1151.
[11]黄丹丹.环维黄杨星D对大鼠心衰的治疗作用及其对心肌Na+-K+-ATPase亚基表达的影响[D].南京:南京中医药大学,2013.