沙棘总黄酮对牵张所致心衰心肌细胞的收缩力学和钙离子转运的影响
作者：王正荣 王玲 尹华虎 杨芳炬 高云钦 张祝君
单位：
关键词：沙棘总黄酮；心肌细胞力学；心力衰竭；钙转运；心肌收缩
航天医学与医学工程000102
摘要：目的 研究沙棘总黄酮在改善心衰状态下心肌细胞收缩功能的作用。方法 体外培养大鼠心肌细胞并通过超负荷培养建立心衰心肌细胞模型，给予心衰心肌细胞不同剂量的沙棘总黄酮，然后检测心肌细胞的收缩力学特性和钙离子转运状况。结果 沙棘总黄酮显示出有增加心肌细胞收缩力的作用，并且这种作用具有量——效关系，其心肌细胞收缩力学参数与沙棘总黄酮的相关系数均在1.0～0.9之间(P<0.001)，而沙棘总黄酮增强心肌细胞收缩力的作用是与细胞内钙离子转运未显示出量效关系。结论 在小剂量范围内，沙棘总黄酮是一种不依赖钙离子内转运而增加心肌细胞收缩力，从而能有效改善心衰的中药。
, 百拇医药
中图分类号：R331.3；R285.5 文献标识码：A
文章编号：1002-0837(2000)01-0006-04
Effect of Total Flavonoids of Hippophae Rhamnoides on Contractile Mechanics and Calcium Transfer in Stretched Myocyte
WANG Zheng-rong,WANG Ling,YIN Hua-hu,YANG Fang-ju,GAO Yun-qin
(School of Basic Medical Sciences,West China University of Medical Sciences,Chengdu,Sichuan 610041)
, 百拇医药
ZHANG Zhu-jun
(Sichuan MEDCO Pharmaceutical Co.,Ltd,Shifang,Sichuan 618400)
Abstract:Objective To study the role of total flavonoids of hippophae rhamnoides in improving contactile function of stretched cardiac myocyte.Method Flavonoids were given to stretched myocytes which were proved their contractile function decline and then myocyte contractile mechanics characteristics and calcium transfer were measured.Result Flavonoids increased myocyte contractility,as indicated by myocyte shortening,velocity of shortening,peak+dL/dt and peak-dL/dt during shortening,in a concentration-dependent manner (r>0.9,P<0.001),and with no relation to the intracellular calcium transfer in the myocytes.Conclusion Flavonoids of the traditional Chinese drug hippophae rhamnoids is effective in improving the contractile function of stretched cardiac myocyte in low dosage.
, http://www.100md.com
Key words:hippophae rhamnoides;myocyte mechanics;heart failure;calcium transient;myocardial contraction
Heart failure is a severe heart disease caused by many factors,such as hypertension,myocardial infarction and so on.There are many ways of treating heart failure,but the effect is limited.Chinese herbs have some special effects of improving congestive heart failure,particularly,regulating homeostasis with little side effect.The flavonoids of hippophae rhamnoides,extracted from the plant named hippophae rhamnoides L.,have been shown to have the effect of improving myocardial ischemia.Clinical trials showed that the flavonoids can improve angina pectoris,ECG of myocardial ischemia and cardiac function[1，2].Zheng et al reported that total flavonoids of hippophae rhamnoides showed different effects on my-ocardial contractility in different doses[3].Large dose of total flavonoids reduced myocardial contractility while small dose of it increased myocardial contractility[3].Most drugs that improve cardiac function and increase positive inotropium have the effect of increasing calcium transfer in the cardiac myocytes[4].
, 百拇医药
The pupose of this study was to further clarify the mechanism of the flavonoids of hippophae rhamnoides in improving cardiac function.
Method
Drugs Total flavonoids containing mainly isorhamnetin and quercetin were extracted from the plant hippophae rhamnoides by Sichuan MEDCO Pharmaceutical Co.,Ltd.The flavonoids(brown powder lot No 19970616) were dissolved in distilled water to 0.1 g.L-1.
, 百拇医药
Preparation of neonatal rat cardiac myocytes Ventricular myocytes from ten male neonatal SD rats (2d old) were prepared by combined enzymatic and mechanical dissociation as described by McDermott[5].The isolated cardiac myocytes were plated in DMEM containing 10% newborn calf serum at a concentration of 2×105 cells per sqare centimeter in culture dishes coated with collagen and incubated for 12 h to allow cardiac fibroblasts to adhere to the culture dishes,and then the culture media with myocytes were transferred into 4 silicon plastic dishes coated with collagen.
, http://www.100md.com
Myocyte model of heart failure After cultured for 48 h,the media were changed and the myocytes in the silicon plastic dishes were given stretching stress by mechanically stretching the culture dishes to an extent of 20% longer than the original.The myocytes were then incubated for 36 h.
Measurement of myocyte contractile mechanics The myocytes,which were isolated from the culture dish and moved into the perfusion chamber,were stimulated by a bipolar field stimulator (RAP Montgomery,London,UK,5 ms pulse width,50 V).The measurement system(Fig.1) consisted of an inverted phase-contrast microscope (Olympus IMT-2,Leeds Precision) coupled to a high speed (240 Hz) CCD camera (Pulnix,TM640,Sunnyvale,CA) and a video-edge detector (VED 103,Crescent Electronics,Sandy UT).The signal of the myocyte action image was transferred to a computer to analyze myocyte contractile mechanical characteristics.The indices included the percent of resting myocyte length,mean velocity of shortening,and positive and negative peak rate of change in myocyte length.In vivo cal-ibration and the myocyte contractile analysis were done by the method of Anand[6].
, http://www.100md.com
Measurement of calcium transfer During the myocyte contractile action caused by the pulse electronic stimulation,the intracellular calcium transfer was measured by the video-edge detector coupled to a dual excitation fluorescence system.The intracellular calcium transfer was indexed by the amplitude of 360/380 nm ratio[7].
Fig.1 Apparatus for measuring the myocyte contractile function and calcium transfer
, http://www.100md.com
Experiment protocol The dose-effect relationship was observed by measuring the contractile mechanics and intracellular calcium transfer of the stretched myocytes under different doses of the flavonoids.The doses were 0,10,20,30,40 and 50 mg.L-1 of the flavonoids in the perfusion fluid of the perfusion chamber.
Statistical analysis Twenty myocytes isolated from the culture dishes were randomly chosen to measure the contractile mechanics and calcium transfer.The ANOVA was used to test the differences between the data before and after given the flavonoids.Correlation and linear regression analysis were used to test the dose-response relationship.
, 百拇医药
Result
Table 1 shows the results of the con-tractile mechanics of the stretched myocytes under different doses of the flavonoids.The parameters of myocyte contractile mechanics included percent of myocyte shortening during contraction,mean velocity of shortening (velocity),positive peak rate of change in myocyte length (+dL/dt) and negative peak rate of change in myocyte length (-dL/dt).The effect of the flavoniods showed a obviously dose-response relation,but no dose-dependent effect on calcium transfer was observed in the dosage range we used (Fig.2).
, 百拇医药
Table 1 Effect of flavonoids of hippophae rhamnoides on myocyte contractile mechanical characteristics and calcium transfer(
±s) indices
Dose of flavonoids of hippophae rhamnoides(mg.L-1)
ANOVA
0
10
20
30
, 百拇医药
40
50
F
P
myocyte shortening(%)
4.0±0.2
4.7±0.3
5.7±0.4
6.5±0.3
7.0±0.4
7.5±0.4
357.2
, 百拇医药
<0.001
Velocity(μm.s-1)
29.9±2.1
36.8±4.6
48.5±5.3
55.8±4.9
61.7±5.4
67.4±6.3
158.5
<0.001
+dL/dt(μm.s-1)
, 百拇医药
40.2±3.3
52.7±4.5
65.7±4.1
78.7±5.8
87.3±5.8
96.7±6.3
353.9
<0.001
-dL/dt(μm.s-1)
28.9±2.7
38.4±4.5
, http://www.100md.com
53.3±5.2
65.5±7.7
74.3±7.6
82.8±7.4
232.4
<0.001
Ratio(360nm/380nm)
0.34±0.04
0.34±0.03
0.36±0.04
0.33±0.04
0.31±0.04
, 百拇医药
0.32±0.03
0.862
>0.05
Myocyte shortening=Percent of myocyte shortening,Velocity=Mean velocity of shortening,+dL/dt=positive peak rate of change in myocyte length,-dL/dt=negative peak rate of change in myocyte length during contraction
Fig.2 Dose-response relationship between the flavonoids and the myocyte contractile mechanics
, 百拇医药
The percentage shortening,velocity,+dL/dt and -dL/dt of myocyte shortening were all positively correlated with the dose of the flavonoids (P<0.001),but the calcium transfer showed a very slight negative relation with the dose (P>0.1).The linear regression equations obtained are showed as follows:
Myocyte shortening=0.0725(dose)+4.1059,r=0.9632,P<0.001
Velocity=0.7359(dose)+32.2786,r=0.9282,P<0.001
, 百拇医药
+dL/dt=1.1400(dose)+41.6833,r=0.9660,P<0.001
-dL/dt=1.1130(dose)+29.3667,r=0.9499,P<0.001
Calcium transient=-0.000317(dose)+0.34649,r=0.0872,P>0.1
Discussion
Therapy of congestive heart failure is a big clinical problem,because there is no effective way to cure it.Therefore,many researchers did lots of studies to find an efficient way or a drug to cure it[7，8].Chinese traditional medicine shows typical effect of treating the heart diseases including congestive heart failure based on the clinical experiences of several thousand years[9].However,the mechanisms of improving cardiac function by these Chinese traditional medicine are still not clear.It has been known that the flavonoids have the effect of improving cardiac function in patients with chronic cardiac dysfunction or myocardial ischemia,and increasing the myocardial contractility of isolated guinea pig papillary muscle[1～3].However,some studies have proved that small dose of the flavonoids increases the myocardial contractility,which high dose reduces it[3].The dosages we used were low,and had a positive effect on the myocyte contractility.It was consistent with Li's results[10].
, 百拇医药
The effect of the flavoniods in increasing myocardial contractility observed in our study maybe due to the low dosage we used.The flavonoids have the effect of inhibiting intracellular calcium transfer in myocardium,which had been proved in the previous study[3],and it was also shown in our study that the flavonoids have a tendency to reduce intracellular calcium transfer,which does not show statistically signifcant relationship between the myocyte contractile function and calcium transfer.Since the dosages we used were small,it could not completely stop the intracellular calcium transfer,and there may still be considerable amount of calcium transferred from the outside of myocyte to its inside.Generally,most positively inotropic drugs increase the myocardial contractility by increasing the intracellular calcium transfer in the myocytes.Our study,however,shows that the myocyte contractility increases when the dose of the flavonoids increases,which is obviously different from the mechanism of inotropic drugs.Basing on the previous studies and our results,we consider that the flavonoids probably have the effect of increasing the calcium in myocyte binding to certain contractile proteins to produce contractile function,or that of increasing ATPase activity of myosin heave chain to promote myocardial contractility.Thus,small dose of the flavonords of this traditional Chinese drug may be ideal in treating chronic cardiac dysfunction and heart failure.In Russia,Hippophae Rhamnoides were widely studied and used to improve astronauts health,we think some of efficient components in Hippophae are flavonoids.Therefore,small dose flavonoids.Therefore,small does flavonoids could be given astronauts,since the astronauts under explosed to weightlessness for long time,would suffer from cardiac function decrease[11，12].
, 百拇医药
To sum up,small doses of the flavonoids have the function of directly increasing myocyte contractility,this effect depends on the dosage.The effect of low dosages of the flavonoids on myocyte contractile function is not related with the intracellular calcium transfer.
Foundation item:This work is supported by National Nature Science Foundation of China(39570311)
[References]
[1]Xia H,Deng K.Analyzing the effect of XINDACOM tablet on angina pectoris[J].Chinese J Cardiovascul,1996,1:53～54
, 百拇医药
[2]Wang Jialiang,Zhang Maoshun,Xu Zhiqi et al.Effect of Flavonoids of Hippophae Rhamnoides L on ischemic heart disease[J].Acta Academiae Medicine Sichuan,1982,13:6～11
[3]Zheng H,Dong Z et al.Modern study of traditional Chinese medicine (Vol 3)[M].Xue Yuan Press,Beijing,Jan,1998:2423～2445
[4]Chen X,Chen W,Zen G.Cardiovascular Pharmacology[M].People's Health Publishing House,Feb 1997:346～285
[5]McDermott PJ,Morgan HE.Contraction modulation the capacity for protein synthesis during growth of neonatal heart cells in culture[J].Circ Res,1989,64:642～553
, 百拇医药
[6]Anand IS,Liu D,Chugh SS et al.Isolated myocyte contractile function is normal in the post infarct remodeled rat heart with systolic dysfunction[J].Circulation,1997,96:3974～3984
[7]Mark DB.Economics of treating heart failure[J].Am J Cardiology,1997,80(8B):33H～38H
[8]Simpson RJ,Sueta CA,Boccuzzi SJ et al.Performance assessment model for guideline-recommended pharmacotherapy in the secondary prevention of coronary artery disease and treatment of left ventricular dysfunction[J].Am J Cardiol,1997,80(8B):53H～56H
, 百拇医药
[9]Qu S,Li J.Applying Chinese traditional medicine in cardiology[M].Seientific and Technologic Article Publishing House.May,1993:209～225
[10]Li K,Wang B,Feng Y.Effect of total flavones of hippophae rhamnoides L on the physiological properties of isolated guinea pig papillary muscle[J].Northwest pharmaceutical J,1994,9:29～31
[11]YHEN Xianyun.Cardiovascular problems during space flight[J].Space Medicine & Medical Engineering,1992，5(4)：295～301
, 百拇医药
沈羡云.航天中的心血管问题[J].航天医学与医学工程，1992，5(4)：295～301
[12]YU Zhibin,XIE Xiaoping,BAO Junxiang et al.Tail-suspended rats with inguinal canal ligation and their myocardial function[J].Space Medicine & Medical Engineering,1998,11(3):172～176
余志斌，谢小萍，暴军香等.雄性无隐睾尾部悬吊大鼠及其心肌功能[J].航天医学与医学工程,1998,11(3):172～176
Recieved date:1999-04-12, 百拇医药
单位：
关键词：沙棘总黄酮；心肌细胞力学；心力衰竭；钙转运；心肌收缩
航天医学与医学工程000102
摘要：目的 研究沙棘总黄酮在改善心衰状态下心肌细胞收缩功能的作用。方法 体外培养大鼠心肌细胞并通过超负荷培养建立心衰心肌细胞模型，给予心衰心肌细胞不同剂量的沙棘总黄酮，然后检测心肌细胞的收缩力学特性和钙离子转运状况。结果 沙棘总黄酮显示出有增加心肌细胞收缩力的作用，并且这种作用具有量——效关系，其心肌细胞收缩力学参数与沙棘总黄酮的相关系数均在1.0～0.9之间(P<0.001)，而沙棘总黄酮增强心肌细胞收缩力的作用是与细胞内钙离子转运未显示出量效关系。结论 在小剂量范围内，沙棘总黄酮是一种不依赖钙离子内转运而增加心肌细胞收缩力，从而能有效改善心衰的中药。
, 百拇医药
中图分类号：R331.3；R285.5 文献标识码：A
文章编号：1002-0837(2000)01-0006-04
Effect of Total Flavonoids of Hippophae Rhamnoides on Contractile Mechanics and Calcium Transfer in Stretched Myocyte
WANG Zheng-rong,WANG Ling,YIN Hua-hu,YANG Fang-ju,GAO Yun-qin
(School of Basic Medical Sciences,West China University of Medical Sciences,Chengdu,Sichuan 610041)
, 百拇医药
ZHANG Zhu-jun
(Sichuan MEDCO Pharmaceutical Co.,Ltd,Shifang,Sichuan 618400)
Abstract:Objective To study the role of total flavonoids of hippophae rhamnoides in improving contactile function of stretched cardiac myocyte.Method Flavonoids were given to stretched myocytes which were proved their contractile function decline and then myocyte contractile mechanics characteristics and calcium transfer were measured.Result Flavonoids increased myocyte contractility,as indicated by myocyte shortening,velocity of shortening,peak+dL/dt and peak-dL/dt during shortening,in a concentration-dependent manner (r>0.9,P<0.001),and with no relation to the intracellular calcium transfer in the myocytes.Conclusion Flavonoids of the traditional Chinese drug hippophae rhamnoids is effective in improving the contractile function of stretched cardiac myocyte in low dosage.
, http://www.100md.com
Key words:hippophae rhamnoides;myocyte mechanics;heart failure;calcium transient;myocardial contraction
Heart failure is a severe heart disease caused by many factors,such as hypertension,myocardial infarction and so on.There are many ways of treating heart failure,but the effect is limited.Chinese herbs have some special effects of improving congestive heart failure,particularly,regulating homeostasis with little side effect.The flavonoids of hippophae rhamnoides,extracted from the plant named hippophae rhamnoides L.,have been shown to have the effect of improving myocardial ischemia.Clinical trials showed that the flavonoids can improve angina pectoris,ECG of myocardial ischemia and cardiac function[1，2].Zheng et al reported that total flavonoids of hippophae rhamnoides showed different effects on my-ocardial contractility in different doses[3].Large dose of total flavonoids reduced myocardial contractility while small dose of it increased myocardial contractility[3].Most drugs that improve cardiac function and increase positive inotropium have the effect of increasing calcium transfer in the cardiac myocytes[4].
, 百拇医药
The pupose of this study was to further clarify the mechanism of the flavonoids of hippophae rhamnoides in improving cardiac function.
Method
Drugs Total flavonoids containing mainly isorhamnetin and quercetin were extracted from the plant hippophae rhamnoides by Sichuan MEDCO Pharmaceutical Co.,Ltd.The flavonoids(brown powder lot No 19970616) were dissolved in distilled water to 0.1 g.L-1.
, 百拇医药
Preparation of neonatal rat cardiac myocytes Ventricular myocytes from ten male neonatal SD rats (2d old) were prepared by combined enzymatic and mechanical dissociation as described by McDermott[5].The isolated cardiac myocytes were plated in DMEM containing 10% newborn calf serum at a concentration of 2×105 cells per sqare centimeter in culture dishes coated with collagen and incubated for 12 h to allow cardiac fibroblasts to adhere to the culture dishes,and then the culture media with myocytes were transferred into 4 silicon plastic dishes coated with collagen.
, http://www.100md.com
Myocyte model of heart failure After cultured for 48 h,the media were changed and the myocytes in the silicon plastic dishes were given stretching stress by mechanically stretching the culture dishes to an extent of 20% longer than the original.The myocytes were then incubated for 36 h.
Measurement of myocyte contractile mechanics The myocytes,which were isolated from the culture dish and moved into the perfusion chamber,were stimulated by a bipolar field stimulator (RAP Montgomery,London,UK,5 ms pulse width,50 V).The measurement system(Fig.1) consisted of an inverted phase-contrast microscope (Olympus IMT-2,Leeds Precision) coupled to a high speed (240 Hz) CCD camera (Pulnix,TM640,Sunnyvale,CA) and a video-edge detector (VED 103,Crescent Electronics,Sandy UT).The signal of the myocyte action image was transferred to a computer to analyze myocyte contractile mechanical characteristics.The indices included the percent of resting myocyte length,mean velocity of shortening,and positive and negative peak rate of change in myocyte length.In vivo cal-ibration and the myocyte contractile analysis were done by the method of Anand[6].
, http://www.100md.com
Measurement of calcium transfer During the myocyte contractile action caused by the pulse electronic stimulation,the intracellular calcium transfer was measured by the video-edge detector coupled to a dual excitation fluorescence system.The intracellular calcium transfer was indexed by the amplitude of 360/380 nm ratio[7].
Fig.1 Apparatus for measuring the myocyte contractile function and calcium transfer
, http://www.100md.com
Experiment protocol The dose-effect relationship was observed by measuring the contractile mechanics and intracellular calcium transfer of the stretched myocytes under different doses of the flavonoids.The doses were 0,10,20,30,40 and 50 mg.L-1 of the flavonoids in the perfusion fluid of the perfusion chamber.
Statistical analysis Twenty myocytes isolated from the culture dishes were randomly chosen to measure the contractile mechanics and calcium transfer.The ANOVA was used to test the differences between the data before and after given the flavonoids.Correlation and linear regression analysis were used to test the dose-response relationship.
, 百拇医药
Result
Table 1 shows the results of the con-tractile mechanics of the stretched myocytes under different doses of the flavonoids.The parameters of myocyte contractile mechanics included percent of myocyte shortening during contraction,mean velocity of shortening (velocity),positive peak rate of change in myocyte length (+dL/dt) and negative peak rate of change in myocyte length (-dL/dt).The effect of the flavoniods showed a obviously dose-response relation,but no dose-dependent effect on calcium transfer was observed in the dosage range we used (Fig.2).
, 百拇医药
Table 1 Effect of flavonoids of hippophae rhamnoides on myocyte contractile mechanical characteristics and calcium transfer(
±s) indicesDose of flavonoids of hippophae rhamnoides(mg.L-1)
ANOVA
0
10
20
30
, 百拇医药
40
50
F
P
myocyte shortening(%)
4.0±0.2
4.7±0.3
5.7±0.4
6.5±0.3
7.0±0.4
7.5±0.4
357.2
, 百拇医药
<0.001
Velocity(μm.s-1)
29.9±2.1
36.8±4.6
48.5±5.3
55.8±4.9
61.7±5.4
67.4±6.3
158.5
<0.001
+dL/dt(μm.s-1)
, 百拇医药
40.2±3.3
52.7±4.5
65.7±4.1
78.7±5.8
87.3±5.8
96.7±6.3
353.9
<0.001
-dL/dt(μm.s-1)
28.9±2.7
38.4±4.5
, http://www.100md.com
53.3±5.2
65.5±7.7
74.3±7.6
82.8±7.4
232.4
<0.001
Ratio(360nm/380nm)
0.34±0.04
0.34±0.03
0.36±0.04
0.33±0.04
0.31±0.04
, 百拇医药
0.32±0.03
0.862
>0.05
Myocyte shortening=Percent of myocyte shortening,Velocity=Mean velocity of shortening,+dL/dt=positive peak rate of change in myocyte length,-dL/dt=negative peak rate of change in myocyte length during contraction
Fig.2 Dose-response relationship between the flavonoids and the myocyte contractile mechanics
, 百拇医药
The percentage shortening,velocity,+dL/dt and -dL/dt of myocyte shortening were all positively correlated with the dose of the flavonoids (P<0.001),but the calcium transfer showed a very slight negative relation with the dose (P>0.1).The linear regression equations obtained are showed as follows:
Myocyte shortening=0.0725(dose)+4.1059,r=0.9632,P<0.001
Velocity=0.7359(dose)+32.2786,r=0.9282,P<0.001
, 百拇医药
+dL/dt=1.1400(dose)+41.6833,r=0.9660,P<0.001
-dL/dt=1.1130(dose)+29.3667,r=0.9499,P<0.001
Calcium transient=-0.000317(dose)+0.34649,r=0.0872,P>0.1
Discussion
Therapy of congestive heart failure is a big clinical problem,because there is no effective way to cure it.Therefore,many researchers did lots of studies to find an efficient way or a drug to cure it[7，8].Chinese traditional medicine shows typical effect of treating the heart diseases including congestive heart failure based on the clinical experiences of several thousand years[9].However,the mechanisms of improving cardiac function by these Chinese traditional medicine are still not clear.It has been known that the flavonoids have the effect of improving cardiac function in patients with chronic cardiac dysfunction or myocardial ischemia,and increasing the myocardial contractility of isolated guinea pig papillary muscle[1～3].However,some studies have proved that small dose of the flavonoids increases the myocardial contractility,which high dose reduces it[3].The dosages we used were low,and had a positive effect on the myocyte contractility.It was consistent with Li's results[10].
, 百拇医药
The effect of the flavoniods in increasing myocardial contractility observed in our study maybe due to the low dosage we used.The flavonoids have the effect of inhibiting intracellular calcium transfer in myocardium,which had been proved in the previous study[3],and it was also shown in our study that the flavonoids have a tendency to reduce intracellular calcium transfer,which does not show statistically signifcant relationship between the myocyte contractile function and calcium transfer.Since the dosages we used were small,it could not completely stop the intracellular calcium transfer,and there may still be considerable amount of calcium transferred from the outside of myocyte to its inside.Generally,most positively inotropic drugs increase the myocardial contractility by increasing the intracellular calcium transfer in the myocytes.Our study,however,shows that the myocyte contractility increases when the dose of the flavonoids increases,which is obviously different from the mechanism of inotropic drugs.Basing on the previous studies and our results,we consider that the flavonoids probably have the effect of increasing the calcium in myocyte binding to certain contractile proteins to produce contractile function,or that of increasing ATPase activity of myosin heave chain to promote myocardial contractility.Thus,small dose of the flavonords of this traditional Chinese drug may be ideal in treating chronic cardiac dysfunction and heart failure.In Russia,Hippophae Rhamnoides were widely studied and used to improve astronauts health,we think some of efficient components in Hippophae are flavonoids.Therefore,small dose flavonoids.Therefore,small does flavonoids could be given astronauts,since the astronauts under explosed to weightlessness for long time,would suffer from cardiac function decrease[11，12].
, 百拇医药
To sum up,small doses of the flavonoids have the function of directly increasing myocyte contractility,this effect depends on the dosage.The effect of low dosages of the flavonoids on myocyte contractile function is not related with the intracellular calcium transfer.
Foundation item:This work is supported by National Nature Science Foundation of China(39570311)
[References]
[1]Xia H,Deng K.Analyzing the effect of XINDACOM tablet on angina pectoris[J].Chinese J Cardiovascul,1996,1:53～54
, 百拇医药
[2]Wang Jialiang,Zhang Maoshun,Xu Zhiqi et al.Effect of Flavonoids of Hippophae Rhamnoides L on ischemic heart disease[J].Acta Academiae Medicine Sichuan,1982,13:6～11
[3]Zheng H,Dong Z et al.Modern study of traditional Chinese medicine (Vol 3)[M].Xue Yuan Press,Beijing,Jan,1998:2423～2445
[4]Chen X,Chen W,Zen G.Cardiovascular Pharmacology[M].People's Health Publishing House,Feb 1997:346～285
[5]McDermott PJ,Morgan HE.Contraction modulation the capacity for protein synthesis during growth of neonatal heart cells in culture[J].Circ Res,1989,64:642～553
, 百拇医药
[6]Anand IS,Liu D,Chugh SS et al.Isolated myocyte contractile function is normal in the post infarct remodeled rat heart with systolic dysfunction[J].Circulation,1997,96:3974～3984
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Recieved date:1999-04-12, 百拇医药