川芎嗪结构修饰产物Liguzinediol对阿霉素致慢性心力衰竭模型大鼠血流动力学的影响
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摘要
目的:探讨川芎嗪结构修饰产物Liguzinediol对阿霉素诱导的慢性心力衰竭(CHF)模型大鼠血流动力学的影响。方法:取SD大鼠腹腔注射2 mg/kg阿霉素复制CHF模型,将造模成功的大鼠采用随机数字表法分为生理盐水组、阳性对照组(去乙酰毛花苷注射液,0.022 5 mg/kg)和Liguzinediol低、中、高剂量组(5、10、20 mg/kg),每组8只,另取8只正常大鼠作为空白对照组(生理盐水)。各组大鼠单次静脉注射相应药物后,通过多道生理记录仪左心室插管记录左心室收缩内压(LVSP)、左心室最大压力上升/下降速度(±dp/dt_(max))、收缩压(SP)、舒张压(DP)、心率(HR)等血流动力学指标,记录时间分别为给药后1、5、10、20、40、60、90、120 min。结果:与空白对照组比较,生理盐水组大鼠的LVSP、+dp/dt_(max)、│-dp/dt_(max)│、SP、HR和给药后120 min的DP均明显降低(P<0.05)。与生理盐水组比较,Liguzinediol低剂量组大鼠给药后5～60 min的LVSP、40～90 min的+dp/dt_(max)、10～40 min的SP均明显升高(P<0.05或P<0.01);Liguzinediol中剂量组大鼠给药后5～90 min的LVSP、10～60 min的SP、10～60 min(20 min除外)的DP均明显升高(P<0.05或P<0.01);Liguzinediol高剂量组大鼠给药后1～120 min的LVSP、5～90 min的+dp/dt_(max)、5～60 min的│-dp/dt_(max)│和SP、40～60 min的DP均明显升高(P<0.05或P<0.01)。结论:单次静脉注射Liguzinediol能显著增强CHF模型大鼠的心肌收缩功能,进而控制或缓解其CHF。
OBJECTIVE:To investigate the effects of ligustrazine structural modification product Liguzinediol on hemodynamics in chronic heart failure(CHF) model rats induced by adriamycin. METHODS:SD rats were given intraperitoneal injection of adriamycin(2 mg/kg)to induce CHF model. Model rats were randomly divided into normal saline group,positive control group(Deacetyl tricyanidin injection,0.022 5 mg/kg) and Liguzinediol low-dose,medium-dose and high-dose groups(5,10,20mg/kg),with 8 rats in each group. Other 8 normal rats were selected as blank control group(normal saline). Each group was given relevant medicine intravenously. The left ventricular systolic pressure(LVSP),maximal rate of rise or drop of left ventricular(±dp/dt_(max)),systolic pressure(SP),diastolic pressure(DP),heart rate(HR)and other hemodynamic indexes were recorded by multichannel physiological recorder at 1,5,10,20,40,60,90,120 min after medication. RESULTS:Compared with blank control group,LVSP,+ dp/dt_(max),│-dp/dt_(max)│,SP,HR and DP at 120 min after medication of normal saline group were decreased significantly(P<0.05). Compared with normal saline group,LVSP at 5-60 min after medication,+dp/dt_(max)at 40-90 min after medication,SP at 10-40 min after medication were increased significantly in Liguzinediol low-dose group(P<0.05 or P<0.01). LVSP at 5-90 min after medication,SP at 10-60 min after medication,DP at 10-60 min(except for 20 min) after medication were increased significantly in Liguzinediol medium-dose group(P<0.05 or P<0.01). LVSP at 1-120 min after medication,+ dp/dt_(max)at 5-90 min after medication,│-dp/dt_(max)│,and SP at 5-60 min after medication,DP at40-60 min after medication were increased significantly in Liguzinediol high-dose group(P<0.05 or P<0.01). CONCLUSIONS:Single intravenous injection of Liguzinediol can significantly enhance ventricular systolic function of CHF model rats so as to control or relieve CHF.
OBJECTIVE:To investigate the effects of ligustrazine structural modification product Liguzinediol on hemodynamics in chronic heart failure(CHF) model rats induced by adriamycin. METHODS:SD rats were given intraperitoneal injection of adriamycin(2 mg/kg)to induce CHF model. Model rats were randomly divided into normal saline group,positive control group(Deacetyl tricyanidin injection,0.022 5 mg/kg) and Liguzinediol low-dose,medium-dose and high-dose groups(5,10,20mg/kg),with 8 rats in each group. Other 8 normal rats were selected as blank control group(normal saline). Each group was given relevant medicine intravenously. The left ventricular systolic pressure(LVSP),maximal rate of rise or drop of left ventricular(±dp/dt_(max)),systolic pressure(SP),diastolic pressure(DP),heart rate(HR)and other hemodynamic indexes were recorded by multichannel physiological recorder at 1,5,10,20,40,60,90,120 min after medication. RESULTS:Compared with blank control group,LVSP,+ dp/dt_(max),│-dp/dt_(max)│,SP,HR and DP at 120 min after medication of normal saline group were decreased significantly(P<0.05). Compared with normal saline group,LVSP at 5-60 min after medication,+dp/dt_(max)at 40-90 min after medication,SP at 10-40 min after medication were increased significantly in Liguzinediol low-dose group(P<0.05 or P<0.01). LVSP at 5-90 min after medication,SP at 10-60 min after medication,DP at 10-60 min(except for 20 min) after medication were increased significantly in Liguzinediol medium-dose group(P<0.05 or P<0.01). LVSP at 1-120 min after medication,+ dp/dt_(max)at 5-90 min after medication,│-dp/dt_(max)│,and SP at 5-60 min after medication,DP at40-60 min after medication were increased significantly in Liguzinediol high-dose group(P<0.05 or P<0.01). CONCLUSIONS:Single intravenous injection of Liguzinediol can significantly enhance ventricular systolic function of CHF model rats so as to control or relieve CHF.
引文
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[13]WANG ZQ,LI YH,LI MH,et al.Analysis of noninvasive hemodynamics in patients with chronic heart failure during different periods[J].Journal of Medical Theory&Practice,2017,30(17):2497-2500.
[14]姜龙军,吴建新,赵容军,等.参附注射液联合丹参川芎嗪注射液治疗慢性肺源性心脏病心力衰竭的临床观察[J].中国药房,2015,26(18):2483-2485.
[15]齐海军,王丽,王祥.血流动力学监测在心力衰竭中的临床应用进展[J].中国老年学,2016,36(3):748-750.
[16]王雪梅,刘佳,付殿斌,等.参附汤萃取液成分对阿霉素致大鼠血流动力学、心肌自噬及凋亡的影响[J].陕西中医药大学学报,2014,37(4):75-78.
[2]单晨啸.Liguzinediol在大鼠体内的药代动力学研究[D].南京:南京中医药大学,2012.
[3]刘峥,卞慧敏,陈龙,等.Liguzinediol对正常大鼠心脏血流动力学的影响[J].中国药学杂志,2009,44(15):1155-1158.
[4]闻侃,刘峥,卞慧敏,等.Liguzinediol的急性毒性[J].中国新药与临床杂志,2011,30(3):234-235.
[5]FARGNOLI AS,KATZ MG,YARNALL C,et al.A pharmacokinetic analysis of molecular cardiac surgery with recirculation mediated delivery ofβARKct gene therapy:developing a quantitative definition of the therapeutic window[J].Journal of Cardiac Failure,2011,17(8):691-699.
[6]杨建业,张迎春,唐俊明,等.阿霉素诱导大鼠心衰模型的建立[J].湖北医药学院学报,2005,24(5):269-271.
[7]CHUNG WB,YOUN HJ.Pathophysiology and preventive strategies of anthracycline-induced cardiotoxicity[J].Korean Journal of Internal Medicine,2016,31(4):625-633.
[8]MITRY MA,EDWARDS JG.Doxorubicin induced heart failure:phenotype and molecular mechanisms[J].Int JCardiol Heart Vasc,2016.DOI:10.1016/j.ijcha.2015.11.004.
[9]DOLINSKY VW.The role of sirtuins in mitochondrial function and doxorubicin-induced cardiac dysfunction[J].Biological Chemistry,2017,398(9):955-974.
[10]NOZAKI N,SHISHIDO T,TAKEISHI Y,et al.Modulation of doxorubicin-induced cardiac dysfunction in tolllike receptor-2-knockout mice[J].Circulation,2004,110(18):2869-2874.
[11]MA Z,TANG Q.CTRP3 protected against doxorubicin-induced cardiac dysfunction,inflammation and cell death via activation of SIRT1[J].中国循环杂志,2017,32(S1):38-47.
[12]王建芝,殷莲华.病理生理学[M].8版.北京:人民卫生出版社,2013:212.
[13]WANG ZQ,LI YH,LI MH,et al.Analysis of noninvasive hemodynamics in patients with chronic heart failure during different periods[J].Journal of Medical Theory&Practice,2017,30(17):2497-2500.
[14]姜龙军,吴建新,赵容军,等.参附注射液联合丹参川芎嗪注射液治疗慢性肺源性心脏病心力衰竭的临床观察[J].中国药房,2015,26(18):2483-2485.
[15]齐海军,王丽,王祥.血流动力学监测在心力衰竭中的临床应用进展[J].中国老年学,2016,36(3):748-750.
[16]王雪梅,刘佳,付殿斌,等.参附汤萃取液成分对阿霉素致大鼠血流动力学、心肌自噬及凋亡的影响[J].陕西中医药大学学报,2014,37(4):75-78.