CN108210487A - Application of the Sodium Houttuyfonate in treatment heart failure and/or antiarrhythmic medicament is prepared - Google Patents
Application of the Sodium Houttuyfonate in treatment heart failure and/or antiarrhythmic medicament is prepared Download PDFInfo
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Abstract
The present invention provides application of the Sodium Houttuyfonate in terms for the treatment of heart failure and/or antiarrhythmic medicament is prepared.The present invention also provides application of the Sodium Houttuyfonate in the convergent force drug for preparing enhancing ventricular muscle cell.Present invention discover that Sodium Houttuyfonate increase L type calcium currents (ICa.L), myocardium shrinkage function obstacle caused by being reduced when can improve heart failure due to the release of sarcoplasmic reticulum calcium.Sodium Houttuyfonate blocks peak sodium current (INa.P), there is the characteristic of I class antiarrhythmic drugs, can also block actinocongestin II (ATX II) and induce increased late Na current (INa.L), have and inhibit INa.LThe potentiality of arrhythmia cordis caused by increase.
Description
Technical field
The invention belongs to Sodium Houttuyfonate technical fields, and in particular to a kind of Sodium Houttuyfonate is preparing treatment heart failure
With the application in antiarrhythmic medicament.
Background technology
Heart failure abbreviation heart failure refers to that obstacle occurs for contractile function and (or) diastolic function due to heart, it is impossible to will
Venous return fully discharges heart, leads to venous system sludging, arterial system hemoperfusion is insufficient, so as to cause the heart
Dirty dyshaemia syndrome shows as pulmonary venous pleonaemia, vena cave extravasated blood in such obstacle disease cluster.Heart failure is not one
Independent disease, but the stage last eventually of heart disease development.Almost all of angiocardiopathy finally can all lead to heart failure
Occur, myocardial damage caused by any reason such as myocardial infarction, cardiomyopathy, haemodynamics overload, inflammation can cause
The variation of cardiac structure and function causes ventricular pump blood and (or) full hypofunction, eventually leads to the generation of heart failure.In addition,
The factors such as infection, digitalis poisoning, pulmonary embolism can also induce heart failure on the basis of underlying heart disease.Heart failure is a kind of incidence
The very high clinical syndrome with the death rate, as one of major issue of serious threat human health.It is clinically right at present
The treatment of heart failure is other than etiotropic Primary Care, and drug therapy is to improving the symptom of heart failure, improving Patients with Cardiac Failure
Life quality also takes up critically important status.Therefore, treating the research and development of heart failure medications has become Current therapeutic cardiac disorder neck
One of mostly important research contents in domain.
Clinically mainly there are diuretics, angiotensin converting enzyme inhibitor for treating the drug of heart failure treatment at present
(ACEI), beta-blocker and cardiotonic etc..Its mechanism of action and the scope of application are as follows：
(1) diuretics
The main function of diuretics is sodium retention when inhibiting heart failure, mitigates venous return and mitigates pulmonary congestion, reduces the heart
Dirty preload and improve heart function, eliminate pulmonary edema and periphery oedema.Suitable for occurring apparent expiratory dyspnea, apparent oedema
Etc. symptoms patients with heart failure.The problems such as diuretics easily causes hypopotassaemia and metabolic alkalosis is used for a long time in patients with heart failure.Belong to this
Class has the medicines such as frusemide, triamterene.
(2) ACEI
ACEI can reduce the generation of angiotensins, and this aspect can reduce vascular resistence, mitigate cardiac afterload and
Alleviate the symptom of heart failure；On the other hand left ventricular remodeling can also be reversed, improves prognosis, reduces the death rate, is treatment mental and physical efforts
Failure choice drug.Full retraction phase patients with heart failure must apply ACEI.Patients with heart failure can lead to low blood using ACEI classes drug
The side effects such as pressure, potassium retention, renal function exacerbation.Belonging to such has the medicines such as enalapril, captopril.
(3) beta-blocker
Beta-blocker, so as to inhibit excessively high neurohormone activity, improves cardiac muscle pine by inhibiting sympathetic activation
The effects that relaxation, increase ventricular filling, reduction myocardial anoxia, significantly improves symptom, left chamber function and the exercise tolerance of patients with heart failure,
Reduce the death rate.Beta-blocker is mainly used for the metastable patients with heart failure of chronic systolic, the state of an illness.Patients with heart failure makes
It can increase the case fatality rate of patient with being reduced or being discontinued after beta-blocker.Belonging to such has the medicines such as Betaloc, bisoprolol.
(4) cardiotonic
Cardiac stimulant class drug has positive inotropic action, can increase myocardial contractive power, improve myocardium blood-pumping function, improve cardiac muscle
Cell metabolism is so as to effectively mitigate the symptom of patients with heart failure.It is apparent increased slow that cardiac stimulant class drug expands diastole for the chambers of the heart
Property congestive heart failure effect is preferable.However the effective dose of digitalis cardiotonic and toxic dose are very close to therefore making
Drug poisoning is easily caused with such drug, leads to the serious consequence for threatening patient vitals.Belonging to such has digoxin, ammonia power
The medicines such as agriculture.
Arrhythmia cordis is since sinoatrial node excitement is abnormal or excitement is resulted from other than sinoatrial node, the conduction of excitement is slow, resistance
Stagnant or conducted through abnormal passage, i.e., the origin of cardiomotility and (or) conductive impairment lead to the frequency and (or) the rhythm and pace of moving things of heartbeat
It is abnormal.Arrhythmia cordis is one group of disease important in angiocardiopathy, it can individually fall ill, also can be with other angiocardiopathies companion
Hair.Whether the cause of disease of its prognosis and arrhythmia cordis inducement, evolving trend, causes serious hemodynamic obstacle related.Arrhythmia cordis
It can be by various organic cardiovascular diseases (such as hypertension, myocardial ischemia and myocardial infarction, myocardial damage), drug poisoning, electrolysis
The factors such as matter and acid-base imbalance cause, and part arrhythmia cordis also can be caused by vegetative nerve functional disturbance.In recent years, although
Very big progress is obtained in the drug therapy of arrhythmia cordis, but the death rate of arrhythmic patients is still higher.Therefore, resist
The research and development of antiarrhythmic medicament have become one of considerable research contents in Current therapeutic cardiac disorder field.
The pathogenesis of arrhythmia cordis is related with the dysfunction of the various transmembrane ion channels of cardiac muscle cell.Wherein, calcium leads to
Road and sodium channel play important function in the electrical activity of cardiac muscle cell, and how associated antiarrhythmic drug is also.The anti-heart
Restraining not normal medicine can directly be combined or the indirectly-acting by receptor etc. with ion channel, become intraor extracellular ion concentration
Change, so as to inhibit the electrical activity of cardiac muscle cell, correct arrhythmia cordis.However, antiarrhymic not only influences abnormal electrical activity,
Also have an impact to normal electrical activity.In addition, (rhythm of the heart is caused to lose since the extra-inhibitory of electrical activity can also generate new arrhythmia cordis
Often effect), by inhibiting ion stream that can also influence myocardial contractive power, many drugs are prohibited in Lower cardiac function or cardiac insufficiency
With.Therefore, antiarrhymic is to be difficult to proper use of drug, but its effectiveness is notable, clinically locates in some sense
In consequence.
The classification of presently used antiarrhythmic drug and mechanism of action：
Very widely used today antiarrhythmic drug is the Vaughan Williams classification improved, according to drug effect
Electrophysiology feature, antiarrhymic can be divided into four classes, wherein I classes medicine is divided into as tri- subclass of A, B, C.
(1) I classes --- sodium channel blocking agent
1.IA class appropriateness block sodium channels, belonging to such has the medicines such as quinindium.
2.IB classes are slight block sodium channels, belonging to such has the medicines such as lidocaine.
The apparent block sodium channels of 3.IC classes, belonging to such has the medicines such as Flecainide.
(2) II classes --- beta-adrenoceptor blocking drug
Beta-adrenoceptor blocking drug is effective when blocking beta receptor, and representative drugs are Propranolol.
(3) Group III --- inhibit a variety of potassium currents, selectively over reach potential duration (APD) and effective refractory period
Medicine
(4) IV classes --- calcium antagonist
Calcium antagonist blocks calcium channel and inhibits Ca2+Interior stream, representative drugs have Verapamil.
Although at present clinically there are many treatment heart failure and the drug of arrhythmia cordis, its effect is limited or has pernicious
Side effect, therefore, research and develop the drug of the relatively small treatment heart failure of novel, effective, side effect and arrhythmia cordis for carrying
The survival rate and quality of life of high patient has considerable meaning.
Cordate houttuynia enjoys great prestige great reputation, and titled with " god grass " title, the life of " being both drug and food " is set to by health ministry
One of goods and materials source, China and south east asia as drug and eat have been subjected to thousands of years as long as, drug effect has obtained very
Good understanding and side effect very little.Therefore for Drug safety and development cost, the anti-heart of houttuynia extract monomer
Better application prospect will be had with antiarrhythmic effect by declining.Sodium Houttuyfonate (C14H27NaO5S, molecular weight 330.41) be
The sodium hydrogensulfite addition product of active ingredient decanoyl acetaldehyde in artificial synthesized natural cordate houttuynia.Sodium Houttuyfonate has extensive
Pharmacological action such as has the effects that anti-inflammatory, antibacterial and Cardioprotective.At present, Sodium Houttuyfonate tablet and Sodium Houttuyfonate note
It penetrates liquid and has been widely used in the clinically treatment for chronic bronchitis, infantile pneumonia and other respiratory inflammation venereal diseases.
Furthermore, it has been reported that in the research carried out using rat as experimental animal, Sodium Houttuyfonate, which has, inhibits myocardial hypertrophy and alleviation
The effect of remodeling ventricle that pressure load induction generates.However, Sodium Houttuyfonate is to mycardial contractility power and cardiac muscle cell
The influence of various ion channel currents has not been reported.Heart failure is in most cases to make cardiac output by myocardial contractive power decline
Body circulation caused by deficiency and pulmonary circulatory stasis.And the various ion channel currents of cardiac muscle cell are the bases of cardiac electrical activity,
Generation and development with heart failure and arrhythmia cordis have relationship closely.Therefore, Sodium Houttuyfonate is to mycardial contractility
The influence of power and the various ion channel currents of cardiac muscle cell is for inquiring into Sodium Houttuyfonate controlling for heart failure and arrhythmia cordis
Treatment effect has very great meaning.
Invention content
Technical problem：The defects of in order to solve the prior art, the present invention provides Sodium Houttuyfonates to prepare treatment mental and physical efforts
Application in terms of failure and/or antiarrhythmic medicament.
Technical solution：The present invention provides Sodium Houttuyfonates to prepare treatment heart failure and/or arrhythmia drug object space
The application in face.
The present invention is tested using purebred new zealand rabbit, by measuring receipts of the Sodium Houttuyfonate to ventricular muscle cell
Contracting power and L-type calcium current (ICa.L), late Na current (INa.L) and peak sodium current (INa.P) effect, it was confirmed that Sodium Houttuyfonate
Have the function of potentially to treat heart failure and arrhythmia cordis.It is specific as follows：
Sodium Houttuyfonate (100 μm of ol/L) can increase shrinkage amplitude, the maximum collapse rate of ventricular muscle cell sarcomere
With maximum relaxation rate, show that Sodium Houttuyfonate can effectively enhance the convergent force of channel in rabbit ventricular myocytes.The present invention carries as a result,
Application of the Sodium Houttuyfonate in the convergent force drug for preparing enhancing ventricular muscle cell is supplied.
Sodium Houttuyfonate (10 μm of ol/L, 50 μm of ol/L and 100 μm of ol/L) increases channel in rabbit ventricular myocytes to concentration dependent
ICa.L, half-maximal effect concentration (EC50) it is 37.10 ± 1.19 μm of ol/L (n=8).Sodium Houttuyfonate (100 μm of ol/L) can also
Slow down ICa.LSteady-state inactivation and accelerate ICa.LInactivation-resurrection process.The present invention provides Sodium Houttuyfonates as a result, to make
Standby increase ventricular muscle cell ICa.LApplication in drug.
Sodium Houttuyfonate (50 μm of ol/L and 100 μm of ol/L) inhibits to concentration dependent channel in rabbit ventricular myocytes by actinocongestin
II (ATX-II) induces increased INa.L, inhibiting rate is respectively 30.1% and 57.1% (n=8).As a result, the present invention provides
Sodium Houttuyfonate is preparing inhibition ventricular muscle cell INa.LIncrease the application in drug.
Sodium Houttuyfonate (1 μm of ol/L, 10 μm of ol/L, 50 μm of ol/L and 100 μm of ol/L) inhibits to concentration dependent the rabbit heart
The I of room myocyteNa.P, 503nhibiting concentration (IC50) it is 78.89 ± 5.68 μm of ol/L (n=9).Sodium Houttuyfonate (100 μm of ol/L)
It can also accelerate INa.PSteady-state inactivation process.The present invention provides Sodium Houttuyfonates as a result, to prepare inhibition ventricular muscle cell INa.P
Application in drug.
Preferably, the drug is capsule, micro-capsule, liposome, granule, parenteral solution, tablet or oral liquid.
Advantageous effect：Present invention discover that Sodium Houttuyfonate increase L-type calcium current (ICa.L), when can improve heart failure
Myocardium shrinkage function obstacle caused by being reduced due to the release of sarcoplasmic reticulum calcium.Sodium Houttuyfonate blocks peak sodium current (INa.P), tool
There is the characteristic of I class antiarrhythmic drugs, can also block actinocongestin II (ATX-II) and induce increased late Na current (INa.L),
It, which has, inhibits INa.LThe potentiality of arrhythmia cordis caused by increase.Therefore, Sodium Houttuyfonate is potential becomes novel, effective
, the drug of side effect is relatively small treatment heart failure and arrhythmia cordis.
1. Sodium Houttuyfonate can enhance the convergent force of cardiac muscle cell, there is the spy of the cardiotonic in treatment heart failure medications
Property, body circulation and pulmonary circulatory stasis caused by myocardial contractive power declines when can directly and efficiently improve heart failure.
2. Sodium Houttuyfonate can increase ICa.L, increase intracellular calcium ion concentration, heart failure can be effectively improved
When due to sarcoplasmic reticulum calcium release reduce caused by myocardium shrinkage function obstacle.
3.INa.LIt will appear abnormal increase under the pathologic conditions such as hypoxic-ischemic, myocardial hypertrophy and heart failure, removed after making morning
It is extremely easy to occur, results even in the malignant arrhythmias such as torsades de pointes.And Sodium Houttuyfonate can press down
ATX-II processed induces increased INa.L, show that it can effectively inhibit the generation of such malignant arrhythmia.
4. under a variety of pathologic conditions such as arterial embolism, myocardial hypertrophy and heart failure, since the electromechanical of cardiac muscle cell is lived
It is dynamic unstable, it is easy to cause the generation of the tachyarrhythmias such as auricular fibrillation.Sodium Houttuyfonate can inhibit INa.P, there is I
The characteristic of class antiarrhythmic drug can reduce the excitability of cardiac muscle cell and effectively inhibit the rapidities heart such as auricular fibrillation
It restrains not normal.
5. many traditional antiarrhythmic drugs are inhibiting ion stream by the way that ion stream performance is inhibited to work
Myocardial contractive power can be also influenced simultaneously, many drugs is resulted in and is disabled in Lower cardiac function or cardiac insufficiency.And cordate houttuynia
Plain sodium can also enhance the convergent force of cardiac muscle while with anti-arrhythmia potentiality, show Sodium Houttuyfonate for heart function not
During full patient, arrhythmia cordis can not only be effectively inhibited, can also effectively improve the heart function of patient.
Therefore, Sodium Houttuyfonate can become novel, effective treatment heart failure and the drug of arrhythmia cordis.
Description of the drawings
Fig. 1 are that Sodium Houttuyfonate enhances result of the test figure to the convergent force of channel in rabbit ventricular myocytes；
Fig. 2 are I of the Sodium Houttuyfonate to channel in rabbit ventricular myocytesCa.LIncrease Experiment on Function result figure；
Fig. 3 are the I that Sodium Houttuyfonate induces ATX-II increased channel in rabbit ventricular myocytesNa.LInhibiting effect result of the test
Figure；
Fig. 4 are I of the Sodium Houttuyfonate to channel in rabbit ventricular myocytesNa.PInhibiting effect result of the test figure.
Specific embodiment
In order to verify the technique effect of the present invention, present embodiment illustrates cordate houttuynia by the research of cellular level
Plain sodium is in the new application of pharmaceutical field.
1 material
1.1 animal
The new zealand rabbit of healthy adult, 1.5~2kg of weight, no matter male and female, by Wuhan University Of Technology's zoopery
The heart provides.
1.2 key instrument
EPC10 patch clamp amplifiers (German Heka Electronic companies)；The dynamic edge detection system (U.S. Ion of visualization
Optix companies)；Three-dimensional micromanipulator (Sutter companies of the U.S.)；Fluorescence inverted microscope (Japanese Nikon companies)；Two step glass
Glass microelectrode draws instrument (Japanese Narishige companies)；Constant speed pump (Baoding Shen Chenbeng industry Co., Ltd).
1.3 drugs and reagent
Purchased from Gibco companies of the U.S., taurine, seralbumin and HEPES are purchased from Switzerland by type i collagen enzyme and CsCl
Roche companies, glutamic acid and taurine are purchased from Central-South institute of biological products, Wuhan, and other drugs are purchased from U.S. Sigma
Aldrich.
1.4 experimental solutions are prepared
(1) perfusate (mmol/L) of ventricular muscle cell convergent force is recorded：NaCl is 131, CaCl2It is 1.8, MgCl2It is 1,
KCl is 4, HEPES 10, glucose 10, with NaOH tune pH value to 7.4.
(2) without calcium tyrode (mmol/L)：NaCl is 135, NaH2PO4For 0.33, KCl 5.4, MgCl2It is 1.0,
HEPES is 10, glucose 10, with NaOH tune PH to 7.4.
(3) KB liquid (mmol/L)：KOH is 70, KCl 40, KH2PO4It is 20, glutamic acid 50, taurine 20, EGTA
It is 0.5, glucose 10, HEPES 10, MgSO4It is 3, with KOH tune PH to 7.4.
(4) I is recordedCa.LElectrode in liquid (mmol/L)：CsCl is 80, CsOH 60, asparatate 40, CaCl2For
0.65, HEPES 5.0, EGTA 10, MgATP 5.0, Creatine Phosphate Sodium 5.0, with CsOH tune PH to 7.3.
(5) I is recordedCa.LAnd INa.LPerfusate (mmol/L)：NaCl is 135, CsCl 5.4, MgCl2It is 1.0, grape
Sugar 10, NaH2PO4It is 0.33, BaCl2For 0.3, HEPES 10, CaCl2It is 1.8, with NaOH tune PH to 7.4.
(6) I is recordedNa.LAnd INa.PElectrode in liquid be (mmol/L)：CsCl is 120, CaCl2It is 1.0, MgCl2It is 5.0,
Na2ATP is 5.0, etamon chloride 10, EGTA 11, HEPES 10, is to adjust PH to 7.3 with CsOH.
(7) I is recordedNa.PPerfusate (mmol/L)：NaCl is 30, CaCl2For 1.0, CsCl 105, MgCl2It is 1.0,
CdCl2For 0.05, HEPES 5.0, glucose 5.0, with CsOH tune PH to 7.4.
2nd, experimental method
2.1st, Ventricular Myocytes are detached using enzymatic isolation method.Select the purebred big ear rabbit of New Zealand of healthy adult, weight
1.5~2kg no matter male and female, after auricular vein injects the abundant anti-freezing of 2000 units of heparin sodium, then injects xylazine
(7.5mg/kg, i.m.) and ketamine (30mg/kg, i.v.) are with sleeping and anesthesia.Then new zealand rabbit is lain on the back binding
It is fixed on rabbit platform, opens chest exposure rapidly and isolates heart, heart is placed in equipped with 37 DEG C of the culture dish without calcium tyrode
In make cardiac arrest, appropriate trimming (removal fat and connective tissue) hangs heart solid by aorta retrograde catheterization
Due on Langendoff perfusion devices, with oxygen saturation, (volume fraction is 95% O2With 5% CO2) and constant temperature (37 DEG C)
Without calcium tyrode perfusion 5min, blood remaining in the chambers of the heart is rinsed well.It is used instead again containing type i collagen enzyme (1g/l) and ox blood
Pure albumen (1g/l) without calcium tyrode row perfusion retrogradely, whole process is continually fed into constant temperature (37 DEG C) and 100% oxygen
Under conditions of carry out, terminate digestion after digestion enzymolysis 30min, use instead and be previously heated to 37 DEG C and 100% oxygen-saturated KB liquid is anti-
5min is rinsed again, so as to which collagen enzyme solution remaining in heart be cemented out, in order to avoid continue to digest.Displacement respectively will after completing
Atrium sinistrum and left ventricle, which shear off, to be put in KB liquid, is shredded ventricular organization in KB liquid and is blown and beaten repeatedly, then through Buddhist nun's chorion mistake
Cell suspension is stored in the KB liquid containing bovine serum albumin(BSA) (1g/l) after filter.It is tested, is tried after standing at least 1 hour
All perfusates are all with the O that volume fraction is 95% in testing2With 5% CO2Saturation and temperature are 37 DEG C.
2.3rd, the contraction of dynamic edge detection system detection ventricular muscle cell is visualized.Cell suspension is instilled to special cell pool
In be placed on the workbench of fluorescence inverted microscope, with perfusate perfusion after cell settlement is adherent, pass through inverted microscope
Selection band is clear, the ventricular muscle cell without vacuole, is recorded with the MyoCam photographic systems of the dynamic edge detection system of visualization slender
Born of the same parents shrink, and present on a monitor.Ventricular muscle cell sarcomere shrinkage amplitude, maximum collapse rate and maximum relaxation rate by
Computer system is acquired, handles and is recorded automatically in real time.
2.4th, the I of whole-cell patch-clamp recording technique record ventricular muscle cellCa.L、INa.LAnd INa.P.Cell suspension is instilled special
Cell pool in be placed on the workbench of fluorescence inverted microscope, with perfusate perfusion after cell settlement is adherent, and laggard
Row whole-cell patch-clamp is tested.Electrode draws instrument by two step glass microelectrodes and draws, and is polished through heat, is filled in electrode after liquid electric
Electrode resistance is 1.5-2.5M Ω.Electric signal is guided through Ag/AgCl electrodes, and meter is stored in by patch clamp amplifier amplification and after filtering
In calculation machine hard disk.
2.5th, data analysis
Data analysis is carried out using Fitmaster, is mapped with Origin8.0 and statistical analysis, all data is used
Mean ± SD is represented.ICa.LAnd INa.PStable state activation and Steady-state inactivation curve Boltzman equation models：Y=1/ [1+
exp(Vm-V1/2)/k], wherein VmRepresent membrane voltage, V1/2Represent that half activation or half inactivation voltage, k represent slope, Y is represented
(Y represents G/G to relative ratio during fitting stable state activation curvemax, Y represents I/I when being fitted steady-state inactivation curvesmax)。ICa.LAnd INa.P
Inactivation-resurrection curve be fitted with exponential function：The time required to I/Imax=1-exp (- t/ τ), wherein t represent to bring back to life, τ is represented
Bring back to life time constant.Current density is calculated by current amplitude/cell capacitance.Compare between two groups of means and (T inspections are examined using T
It is a kind of hypothesis testing method for statistically carrying out two groups of means and comparing to test), compare using variance analysis, P between multigroup mean<
0.05 indicates significant difference.
3rd, result
3.1st, effect of the Sodium Houttuyfonate to ventricular muscle cell convergent force.
By be placed in a pair of parallel platinum electrode of cell trench bottom into line frequency be 0.5Hz, the electricity of pulsewidth 4ms, 35V
MyoCam photographic systems record Ventricular Myocytes contraction change image can be used in field stimulation.Fig. 1 is Sodium Houttuyfonate pair
Ventricular muscle cell convergent force enhances result of the test figure；Wherein：A is control group ventricular muscle cell sarcomere contractible graph, and B is 100 μ
Mol/L Sodium Houttuyfonate intervention group ventricular muscle cell sarcomere contractible graphs, C are again filling group (with the perfusion without Sodium Houttuyfonate
Liquid fills again) ventricular muscle cell sarcomere contractible graph, D, E and F are that Sodium Houttuyfonate shrinks width to ventricular muscle cell sarcomere respectively
The block diagram that degree, maximum collapse rate and maximum relaxation rate influence.As can be seen from Figure 1：Sodium Houttuyfonate can be effectively
Enhance the convergent force of ventricular muscle cell.
3.2nd, Sodium Houttuyfonate is to ventricular muscle cell ICa.LEffect
When Clamping voltages are -40mV, apply one to ventricular muscle cell and depolarized from -40mV with 5mV steps to+60mV
Voltage pulse, continue 300ms, I can be recorded in frequency 0.5HzCa.L。ICa.LThere are run down phenomenons (with the record time
Continuity, the phenomenon that channel current is gradually reduced), then generally persistently 5min tends towards stability, the basicly stable time is 15min.
Therefore, in research Sodium Houttuyfonate to ICa.LEffect when, correlation test should be carried out within this section of stabilization time.
In research Sodium Houttuyfonate to ventricular muscle cell ICa.LWhen concentration dependent acts on, after drug effect stabilization
(2min) could add in next acute drug.Fig. 2 is Sodium Houttuyfonate to ventricular muscle cell ICa.LIncrease Experiment on Function result
Figure；Wherein：A is control group map of current, and B is 10 μm of ol/L, 50 μm of ol/L and 100 μm of ol/L Sodium Houttuyfonate intervention group electric currents
Figure, C are the Sodium Houttuyfonate of various concentration to ventricular muscle cell ICa.LThe I-V curve of influence, D are Sodium Houttuyfonate to ventricular muscles
Cell ICa.LIncrease curve, E be control group and 100 μm of ol/L Sodium Houttuyfonate intervention group ventricular muscle cells ICa.LSteady-state inactivation
Map of current, F are 100 μm of ol/L Sodium Houttuyfonates to ventricular muscle cell ICa.LStable state activation and Steady-state inactivation influence song
Line, G are control group and 100 μm of ol/L Sodium Houttuyfonate intervention group ventricular muscle cells ICa.LInactivation-resurrection map of current, H are 100 μ
Mol/L Sodium Houttuyfonates are to ventricular muscle cell ICa.LThe curve that influences of inactivation-resurrection process.As can be seen from Figure 2：Cordate houttuynia
The increase ventricular muscle cell I of plain sodium energy concentration dependentCa.L；Sodium Houttuyfonate increase ventricular muscle cell ICa.LEC50It is 37.10
± 1.19 μm of ol/L (n=8).In addition, from Fig. 2 it is also seen that：100 μm of ol/L Sodium Houttuyfonates can make ventricular muscle cell
ICa.LSteady-state inactivation curves V1/2From -27.13 ± 0.24mV be displaced to -23.23 ± 0.36mV (n=7, compared with the control group
P ＜ 0.01), k becomes 5.82 ± 0.36 (p compared with the control group from 5.78 ± 0.24>0.05).In addition to this, may be used also from Fig. 2
To find out：100 μm of ol/L Sodium Houttuyfonates can make ventricular muscle cell ICa.LInactivation-resurrection curve τ from 691.69 ±
23.65ms becomes 379.13 ± 12.65ms (n=7, compared with the control group p ＜ 0.01).The result shows that Sodium Houttuyfonate can not only
Increase to concentration dependent ventricular muscle cell ICa.L, moreover it is possible to make ventricular muscle cell ICa.LInactivation curve deviate to the right, inactivation slows down
And ICa.LInactivation-resurrection deactivation time constant reduce, bring back to life and accelerate.
3.3rd, Sodium Houttuyfonate is to ventricular muscle cell INa.LEffect
Clamping voltages be -90mV when, to ventricular muscle cell apply one from -80mV with 10mV steps depolarize to+
The voltage pulse of 60mV, continues 300ms, and I can be recorded in frequency 0.5HzNa.L, its size is measured in 200ms.It is grinding
Study carefully Sodium Houttuyfonate and increased ventricular muscle cell I is induced to ATX-IINa.LWhen concentration dependent acts on, after drug effect stabilization
(2min) could add in next acute drug.Fig. 3 induces increased ventricular muscle cell I for Sodium Houttuyfonate to ATX-IINa.L
Concentration dependent inhibits result of the test figure；Wherein：A is control group map of current, and B is 10nmol/L ATX-II intervention group map of current,
C and D is respectively that 50 μm of ol/L and 100 μm of ol/L Sodium Houttuyfonates induce increased I to ATX-IINa.LIntervention group map of current, E
It is 50 μm of ol/L and 100 μm of ol/L Sodium Houttuyfonates to I under control caseNa.LIntervention group map of current, F be various concentration fish
The plain sodium of raw meat grass induces increased ventricular muscle cell I to ATX-IINa.LThe I-V curve of influence.As can be seen from Figure 3：Decanoy acetaldehyde
The inhibition ATX-II of sodium energy concentration dependent induces increased ventricular muscle cell INa.L；50 μm of ol/L and 100 μm of ol/L cordate houttuynias
Plain sodium induces increased ventricular muscle cell I to ATX-IINa.LInhibiting rate be respectively 30.1% and 57.1%.
3.4th, Sodium Houttuyfonate is to ventricular muscle cell INa.PEffect
When Clamping voltages are -90mV, apply one to ventricular muscle cell and depolarized from -70mV with 5mV steps to+40mV
Voltage pulse, continue 300ms, I can be recorded in frequency 0.5HzNa.P.In research Sodium Houttuyfonate to ventricular muscle cell
INa.PWhen concentration dependent acts on, after drug effect stabilization (2min), next acute drug could be added in.Fig. 4 is fish raw meat
Careless element sodium is to ventricular muscle cell INa.PInhibiting effect result of the test figure；Wherein：A is control group map of current, and B is 10 μm of ol/L, 10 μ
Mol/L, 50 μm of ol/L and 100 μm of ol/L Sodium Houttuyfonate intervention group map of current, C are the Sodium Houttuyfonate of various concentration to ventricle
Myocyte INa.PThe I-V curve of influence, D are Sodium Houttuyfonate to ventricular muscle cell INa.PSuppression curve, E be control group and 100
μm ol/L Sodium Houttuyfonate intervention group ventricular muscle cells INa.PSteady-state inactivation map of current, F are 100 μm of ol/L Sodium Houttuyfonates to the heart
Room myocyte INa.PStable state activation and the curve that influences of Steady-state inactivation, G done for control group and 100 μm of ol/L Sodium Houttuyfonates
Pre- group ventricular muscle cell INa.PInactivation-resurrection map of current, H are 100 μm of ol/L Sodium Houttuyfonates to ventricular muscle cell INa.PMistake
The curve that work-resurrection process influences.As can be seen from Figure 4：The inhibition ventricular muscle cell of Sodium Houttuyfonate energy concentration dependent
INa.P；Sodium Houttuyfonate inhibits ventricular muscle cell INa.PIC50For 78.89 ± 5.68 μm of ol/L (n=9).In addition, from Fig. 4
It is also seen that：100 μm of ol/L Sodium Houttuyfonates can make ventricular muscle cell INa.PSteady-state inactivation curves V1/2From -81.49
± 0.16mV is displaced to -89.65 ± 0.20mV (n=7, compared with the control group p ＜ 0.01), and k becomes 8.16 from 8.80 ± 0.16
± 0.20 (p compared with the control group>0.05).The result shows that Sodium Houttuyfonate can not only inhibit ventricular muscle cell to concentration dependent
INa.P, moreover it is possible to make ventricular muscle cell INa.PInactivation curve deviate to the left, inactivation accelerate.
In conclusion Sodium Houttuyfonate can be in the application in terms of preparation treatment heart failure medications；The drug is capsule, micro-
Capsule, liposome, granule, parenteral solution, tablet or oral liquid.
It should be understood that for those of ordinary skills, can be improved or converted according to the above description,
And all these modifications and variations should all belong to the protection domain of appended claims of the present invention.
Claims (6)
1. application of the Sodium Houttuyfonate in treatment heart failure and/or antiarrhythmic medicament is prepared.
2. application as described in claim 1, it is characterised in that：The drug is capsule, micro-capsule, liposome, granule, injection
Liquid, tablet or oral liquid.
3. application of the Sodium Houttuyfonate in the convergent force drug for preparing enhancing ventricular muscle cell.
4. Sodium Houttuyfonate is preparing increase ventricular muscle cell ICa.LApplication in drug.
5. Sodium Houttuyfonate is preparing inhibition ventricular muscle cell INa.LIncrease the application in drug.
6. Sodium Houttuyfonate is preparing inhibition ventricular muscle cell INa.PApplication in drug.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109223744A (en) * | 2018-11-08 | 2019-01-18 | 上海应用技术大学 | Sodium Houttuyfonate is in preparation for preventing and treating the application in diabetic cardiopathy product |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101618032A (en) * | 2008-07-04 | 2010-01-06 | 上海中医药大学 | Application of sodium houttuyfonate in preparing medicament for preventing and treating myocardial hypertrophy and/or ventricular hypertrophy |
| CN103156842A (en) * | 2013-03-08 | 2013-06-19 | 南开大学 | Novel application of Arctigenin in preparation of anti-arrhythmia medicine |
-
2018
- 2018-03-02 CN CN201810173762.XA patent/CN108210487A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101618032A (en) * | 2008-07-04 | 2010-01-06 | 上海中医药大学 | Application of sodium houttuyfonate in preparing medicament for preventing and treating myocardial hypertrophy and/or ventricular hypertrophy |
| CN103156842A (en) * | 2013-03-08 | 2013-06-19 | 南开大学 | Novel application of Arctigenin in preparation of anti-arrhythmia medicine |
Non-Patent Citations (2)
| Title |
|---|
| JIAN PING GAO ET AL: "Effect of sodium houttuyfonate on inhibiting ventricular remodeling induced by abdominal aortic banding in rats" * |
| JIAN PING GAO ET AL: "Effect of sodium houttuyfonate on myocardial hypertrophy in mice and rats" * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109223744A (en) * | 2018-11-08 | 2019-01-18 | 上海应用技术大学 | Sodium Houttuyfonate is in preparation for preventing and treating the application in diabetic cardiopathy product |
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