CN104688751A - Application of polydatin to preparation of anti-arrhythmic product - Google Patents
Application of polydatin to preparation of anti-arrhythmic product Download PDFInfo
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- CN104688751A CN104688751A CN201510128222.6A CN201510128222A CN104688751A CN 104688751 A CN104688751 A CN 104688751A CN 201510128222 A CN201510128222 A CN 201510128222A CN 104688751 A CN104688751 A CN 104688751A
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- polydatin
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Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides an application of polydatin to preparation of an anti-arrhythmic product and relates to the applications of the polydatin which is a polygonum cuspidatum extract. In-vitro study and experiment results show that the polydatin has a powerful protection function on arrhythmia, and therefore the polydatin can be applied to the preparation of anti-arrhythmic products. According to the application, the polydatin shortens the action potential duration (APD) of myocardial cells by increasing the density of an instant transient outward potassium current (Ito), QT interval prolongation is restrained, and therefore the anti-arrhythmic function is achieved.
Description
Technical field
The application of the active ingredient that the present invention relates to Chinese crude drug in clinical, relate generally to a kind of Chinese medicine extract and polygonin (piceid, polydatin) is being prepared arrhythmia product, particularly prepared the purposes in anti-infarction institute proarrhythmia product.
Background technology
1, arrhythmia
Arrhythmia is because the exciting exception of sinuatrial node or excitement result from beyond sinuatrial node; exciting conduction slowly, retardance or through abnormal passage conduction, namely the origin of cardiomotility and (or) conductive impairment cause frequency and (or) the allorhythmia of heartbeat.Arrhythmia is one group of disease important in cardiovascular disease.It can be fallen ill separately and also can occur together with cardiovascular diseases.Can break out and cause sudden death, also sustainablely involving heart and exhaustion.
Myocardial infarction is a kind of common cardiovascular disease, and it can concurrent dissimilar arrhythmia.Myocardial infarction (having another name called myocardial infarction) is coronary occlusion, can cause blood flow ceases, makes part cardiac muscle, because of serious persistency ischemia, local necrosis occur.Myocardial infarction causes one of main causes of death, is exactly fatal arrhythmia.In the differentiation of the myocardial infarction course of disease and various treatment means application process, all can concurrent dissimilar arrhythmia.Wherein, it is the major reason causing ventricular arrhythmia that transient outward potassium (Ito) dysfunction caused by ischemia and locular wall heterogeneity increase, and the acquired long Q-T interval syndrome caused thus, cause an independent hazard factor of sudden cardiac death especially.
The arrhythmia occurred after myocardial infarction mainly causes due to cardiac electrophysiology reconstruct.Identical of viewsly at present to think, myocardial ischemia causes subunit (Kv4.2, Kv4.3) down-regulated expression of ventricular repolarization ion channel Ito, Ito electric current density is reduced, by extending Single Cardiac Cell, cause long QT syndrome, thus cause the generation of ventricular arrhythmia.
Ito depolarization is activated in early days, and it is expressed and function occurs abnormal.Its feature is mainly: 1) functionally recoverable myocardial cell is more in Reperfu-sion district, and arrhythmia incidence rate is higher.2) ischemic myocardium quantity is many, and degree of ischemia is heavy, Reperfu-sion speed is fast, and the incidence rate of arrhythmia is just high.3) arrhythmia is in the majority with ventricular arythmia.
The antiarrhythmic drug used clinically at present and develop is according to the influence and effect mechanism classification to cardiac electrophysiology, four large classes can be divided into: I class is sodium channel inhibitor, however serious sinus bradycardia, atrioventricular block can be produced, QRS ripple is broadening brings out the side effect such as new torsades de pointes ventricular arrhythmia.II class is beta-blocker, and its side effect is severe hypotension, and also has the effect extending Q-T interval.III class is the medicine that selectivity extends Single Cardiac Cell time-histories (APD) and effective refractory period (ERP), and selectivity blocks the medicine of myocardium potassium-channel, has the side effect similar with I class medicine.IV class is calcium channel blocker.I, II, IV class medicine all has reduction conduction velocity even to cause the effect of conduction block, and these effects can increase the probability of reciprocal excitation, and bring out arrhythmia.III class medicine has no significant effect self-disciplining.
2, Rhizoma Polygoni Cuspidati
Rhizoma Polygoni Cuspidati, originates in East Asia Region, is distributed in the ground such as Jiangsu, Jiangxi, Shandong, Sichuan of the area on the south Hokkaido, Japan western part, the Korea peninsula, Taiwan and China.Mildly bitter flavor, cold nature, containing polygonin, flavone etc.The polygonin used in the present invention can extract in conventional manner, and such as publication number is the extracting method disclosed in the patent in CN1546503A (publication date on November 17th, 2004).The polygonin aqueous solution used in the present invention is prepared in conventional manner, and such as publication number is the method disclosed in the patent of CN1709269A (publication date 2005 on December 21).The concentration of preparation is 6-150mg/ml, and preferred concentration is 20-100mg/ml, and most preferable concentrations is 40mg/ml.
It is found that Rhizoma Polygoni Cuspidati has good potential applicability in clinical practice in recent years, become new study hotspot gradually.In the traditional medicine treatment of motherland, Chinese medicine is owing to being taken from natural plants, and toxic and side effects is few, often has multiple action target spot, and in steady regulation and control, have at body that " high person presses down it, sinking of QI of ZANG FU-organs should be treated by elevation; Have Yu person to damage it, treating deficiency syndrome by tonifying " profoundness.
Polygonin is a kind of monomer extracted in Rhizoma Polygoni Cuspidati, and it is the product that resveratrol is combined with glucose, and they all belong to the stilbene compound in Rhizoma Polygoni Cuspidati composition, i.e. hydroxy stibene compounds.The pharmacological research progress of polygonin cardiovascular aspect comprises:
1) polygonin myocardial cell protection effect.Polygonin is found obviously to alleviate murine myocardium viral infection infringement (Song Junhua, Binzhou Medical College's journal 2008,31:95-98).Domestic scholars report polygonin has the function of the similar resveratrol such as antioxidation, antiinflammatory, and improves effect (the Hebei medicine 2010,32:1492-1493 of cardiac function that hemorrhagic shock causes and microcirculation disturbance; ClinHemorheolMicrocirc.2003,29:211-217).At present, polygonin injection is in IIb phase clinical human conceptual phase at home at present, and IIb phase clinical human progress is smooth.Domestic now current common dose is 50-40mg/kg.
2) polygonin atherosclerosis.Experiment shows, polygonin significantly can reduce the blood fat of Corn Bract Decotion, and can alleviate aorta and the coronary atherosclerosis course of disease.(Chinese tcm emergency, 2005,14:564-567) polygonin also can reduce the soft speckle quantity of the unstable plate of carotid artery, may have the effect (Beijing Chinese medicine, 2009,28172-175) of arteriosclerosis.
3) polygonin antithrombus formation.Polygonin has the Platelet Aggregation in Rabbit suppressing the induction of arachidonic acid, adenosine diphosphate (ADP) and epinephrine in vivo and in vitro, and inhibition strength weakens (Dan Chunwen along with the reduction of polygonin concentration, Acta Pharmacologica Sinica, 1990,11 (6): 527).
Summary of the invention
At present, all antiarrhythmic drugs all have arrhythmogenic effect, and its incidence rate is 6% ~ 36%, its mechanism and electrocardio get excited formed or conductive impairment relevant.Easily occur long Q-T interval syndrome except after myocardial infarction damage, causing in the medicine of long Q-T interval syndrome various, but the most often there is this side effect in antiarrhythmic drug.Object of the present invention, is application polygonin treatment arrhythmia, significantly can reduces the Q-T interval of prolongation, reduce ARR generation.
The present invention includes:
Polygonin is preparing the purposes in arrhythmia product.Described arrhythmia is caused by myocardial infarction.
Polygonin suppresses the purposes in long Q-T interval syndrome product in preparation.Described long Q-T interval, is caused by myocardial infarction.
Polygonin is expressing the purposes in product for the preparation of increase Ito channel protein.Described Ito channel protein is one or more in Kv4.2, Kv4.3 and Kchip.
Polygonin has suppression myocardial infarction and causes Arrhythmia under low dosage (20mg/kg) condition.
The said goods comprises the one in medicine, reagent or food, its occupation mode comprise be used alone or with other chemical substance conbined usage.
Technique effect of the present invention is as follows:
1, in numerous treatment antiarrhythmic medicament, a kind of efficient, cheap and Chinese medicine of safety is chosen, this Chinese medicine (polygonin) can raise transient outward potassium, by potential duration under reach (APD), play antiarrhythmic effect.Polygonin can be used for the treatment of the arrhythmia that myocardial infarction causes especially.
2, provide a kind of and suppress the efficient, cheap of long Q-T interval syndrome and the Chinese medicine of safety, this Chinese medicine (polygonin) is by the adjustment to myocardial cell membrane potassium-channel, regulate the process of repolarization of myocardial cell AP, shorten APD, suppress the generation of long QT syndrome.
3, the efficient, cheap of a kind of protein expression of remarkable increase Ito passage is provided and the Chinese medicine of safety, this Chinese medicine (polygonin) has inhibitory action to myocardial cell membrane Transient Outward Potassium Current (Ito) electric current, significantly increases the protein expression of Ito passage.
4, provide a kind of new low dosage concentration, 20mg/kg, has antiarrhythmic effect.
Accompanying drawing explanation
Fig. 1 is the electrophoretogram of the protein expression representing Ito subunit Kv4.2 and Kchip.
Detailed description of the invention
1. materials and methods
1.1 material
1) polygonin used in reagent the present invention is provided by Hai Wang Pharma Inc. of Shenzhen,
Concrete extracting method is as follows:
Giant knotweed rhizome 100g, suitably pulverizes, and extracts with 800ml ethanol percolation, filter, concentrating under reduced pressure (50 DEG C, 0.07-0.1Mpa), to final volume 50ml, adds 100ml water, and extract 3 times with 200ml vinyl alcohol, extract concentrating under reduced pressure (50 DEG C, 0.07-0.1Mpa) is to 150ml, and Silon stirs, decompression volatilizes solvent, for subsequent use as loading sample.
Loading sample uses a dry method on a sample on polyamide column for subsequent use (cylinder is about 600ml), chromatographic elution is carried out for mobile phase successively with 1000ml water, 3000ml30% ethanol water, flow velocity 600ml/hr, collect 30% ethanol water elution effluent, and will wherein merge containing polygonin stream part, be evaporated to 100ml (60 DEG C, 0.07-0.1Mpa), sucking filtration, draws product 2g, and wherein Determination of Polydatin is 84%.
Head product is with 95-100% dissolve with ethanol, and filter, filtrate adds water to containing alcohol final concentration 30%, add 1% (ml/ml) medical active powdered carbon and boil 3 minutes, filtered while hot, filtrate reduced in volume, to 50ml, leaves standstill 0.5 hour crystallize at 4 DEG C, filter, gained crystal vacuum drying 4 hours (100 DEG C, 0.08-0.1Mpa, phosphorus pentoxide desiccant), obtain end-product polygonin 1.5g, detect containing polygonin 99.82% through HPLC.
Gained polygonin is made into polygonin aqueous solution, and concentration is 40mg/ml.Concrete grammar is as follows: polygonin 11g, propylene glycol 18ml, ethanol 116ml, pure water 200ml, 40 DEG C of ultrasonic dissolutions, 0.45um filtering with microporous membrane, be packed as 100 for subsequent use.Concentrated during use or diluted and obtained aimed concn.
2) Animals Male C57 mice, body weight 25-30g, is provided by Guangdong Province's Experimental Animal Center, totally 60, is divided into sham operated rats, operation group and treatment group at random, often organizes 20 mices.Threading not ligation when sham operated rats is ligation; Operation group is myocardial infarction group; Treatment group is myocardial infarction and gives polygonin gavage treatment group.
3) liquid (mM) in operation of recording potential electrode: KCl 140, MgCl
21, K
2aTP 5, Hepes 5, Glucose 10, KOH adjust pH to 7.4, and 0.22 μm of filtering with microporous membrane subpackage-20 DEG C saves backup.
The preparation (mM) of record Ito electric current extracellular fluid: NaCl 126, KCl 4, MgCl2 2.5, Hepes5, dextrose 5.5, CdCl
20.3, MnCl
22, TEACl 20 (pH 7.3 with NaOH).
1.2 method
1) experiment grouping
Preoperatively give atropine 0.01mg/kg intramuscular injection, with 2% without barbital sodium 60mg/kg, through intraperitoneal injection of anesthesia.Anaesthetize successfully, tracheal intubation, utilize toy respirator to maintain normal respiratory rate (130-150 beat/min) and tidal volume (150-200 ml/min).Record normal II lead electrocardiogram (ECG).Conventional walk abreast tracheal intubation, malleation human assistance of tracheotomy of implementing is breathed.0.5cm place on the left of rat parasternal, 4-5 intercostal, is separated pectoralis major above and pectoralis minor, cuts off Intercostal muscle, then open thoracic cavity with chest expander.After entering pleural space, open pericardium, left anterior descending coronary artery (Left anterior descending between arterial cone and left auricle, LAD) place's threading, except sham operated rats, all the other each group in the drop-down tight knot binding of LAD, upper thread bar is made to oppress LAD, cause bloodstream blocking (alarm with ECGII ST-segment 0.1mV or T wave height, myocardium color becomes white, successfully indicates as LAD ligation).Except sham operated rats and model group adopt normal saline gavage, treatment group adopts the capable gavage treatment of the dosage of 20mg/kg, and second day after operation starts, once a day.Treat after 7 days, recording ecg (QT interval), ultrasound detection cardiac function, leaves and takes serum, and myocardial cell protein extraction detects Ito protein content, another separating myocardium cell, detects AP, record Ito function.
2) electrocardiographic recorder and QT QT dispersion (AD company electrocardiographic recorder) are measured:
Simulation human body crosslinking electrode placement location, utilizes needling electrode to insert animal foot and front subcutaneous record 12 Lead Synchronous ECG.Record 12 lead electrocardiogram respectively at behind preoperative and postoperative 7 days, same continuous measurement 3 cardiac cycles that lead are averaged and are measured QT interval, and QT interval is measured from QRS starting point (as without Q ripple, then with R ripple starting point) to T ripple terminal.Measure difference and lead the longest QT (QTmax) and the shortest QT (QTmin), the QT (QTc) that heart rate corrects with Bazzets formula correction, QT=QT/ (R-R)
1/2, the QT QT dispersion QTcd=QTcmax-QTcmin that heart rate corrects.
3) Heart Brightness Mode Function detection:
Be fixed on after mouse anesthesia on operation panel, instrument adopts dimension victory 2000 toy Ultrasound Instrument.Get minor axis B ultrasonic and M to surpass, the Blind Test 3 times respectively of every mice, averages, calculates left ventricular ejection fraction (LVEF) and evaluate cardiac function.
4) myocardial cell is separated
Anesthesia fully, open rapidly breast and take out heart, be put in the calcium liquid of 0 DEG C and wash, isolate aorta, aorta is inserted gently with No. 7 syringe needles of the ready 10ml of being connected in syringe, aorta is fixed with surgical thread, threeway on Langendorff pipe is opened, liquid flows out, fixing heart No. 7 syringe needles are connected on Langendorff pipe, with there being calcium liquid perfusion, add without calcium liquid, until cardiac arrest, the collagenase and albumin mixed liquor that prepare in advance within 10 ~ 20 minutes, is added after stoping jumping, about 30min heart lighter, during quality deliquescing, getting a little right side myocardium tissue is put in krebs solution, in time having cell to get off, residual myocardium tissue is taken off, surrounding tissue is cut gently with shears, do not cut off, then tissue is put in krebs solution and blows and beats with suction pipe, during piping and druming, cell gets off, and tissue keeps intact form relatively good relatively, blow and beat cell, residue tissue is thrown away, myocardial cell is kept in krebs solution.To stablize after one hour stand-by. mouse cardiac myocytes digestion duration is greatly about 30 ~ 50 minutes.
5) Ito Function detection (full cell pattern recording film electric current)
Experiment glass microelectrode microelectrode draws instrument and divides five steps to draw, then carries out polishing operation, and tip diameter is 0.5-1 μm.Add the magnetic bead of CD8 antibody treatment after cell transfecting 24h, be placed in incubator and hatch 30min, clean for several times with the PBS liquid containing 0.6%FBS before magnetic bead uses.The cell (being the successful cell of transfection) cell membrane being stained with several magnetic bead is selected to carry out electro physiology experiment.Cell incubation liquid adopts tyrode, and electrode charges electrode solution.Electrode is slowly immersed extracellular fluid by operation narishige, imposes a little malleation before entering liquid level, to prevent the foreign material blocking eletrode tip in liquid.After electrode enters water, measurement electrode impedance is at 2-5M Ω proper (resistance excessive or too small be all unfavorable for the formation of full cell and cause rupture of membranes success rate to decline).Return to zero take whole-cell recording technique mode under voltage clamp under, after forming G Ω level high resistance seals, carry out fast capacitance compensation, then controlled underbalance a little, form duct in the plasma membrane of rupture of membranes rear electrode sealing-in, form high resistance seals.Run the protocol set and namely give different voltage stimulations, current signal guides through Ag-AgCl electrode, adopt Axon company of U.S. patch clamp amplifier Axopatch 200B, filtering (frequency 2kHz), at room temperature (22 ~ 25 DEG C) make off-line analysis with Clampex 7.0 acquisition channel current storage after computer.
6) AP detects (under full cell pattern operation of recording current potential)
After forming full cell sealing-in, after liquid in electrode and intracellular fluid balance 3-5min, the wide 1ms of ripple is set, frequency 1Hz, stimulates with the square wave of 800pA, 5ms, the generation of induction action potential.Pulse continued stimulus 10 times, stimulus intervals is 1s.Pulse signal is by clamp software control, by the glass microelectrode transfered cell of liquid in Ag-AgCl wire electrode and filling electrode after amplifier amplifies, the current signal produced is changed through amplifier and is stored in hard disc of computer, analyze the various parameters of action potential, comprise resting potential (RP), overshoot (OS), amplitude of action (APA), repolarization 50% (APD
50) and 90% (APD
90) time.
2. experimental result
2.1 myocardial infarction models are preoperative and respectively organize the ratio of generation chamber arrhythmia and the change of QTcd afterwards in postoperative 7 days
Cardioelectric monitor result display in postoperative seven days, ischemia heart infarction group generation chamber arrhythmia is 15 examples (75%), and polygonin treatment group generation chamber arrhythmia is 5 examples (20%), is obviously less than heart infarction group.As shown in table 1 below, preoperative at myocardial infarction, the more equal no significant difference of QTcd (p>0.05) between 3 treated animals.Ischemia group after surgery more preoperative QTcd obviously increases (p<0.05), and postoperative ischemia group comparatively matched group QTcd also obviously increases (p>0.05).Rhizoma Polygoni Cuspidati treatment group postoperative 7 days QTcd slightly increase, but not statistically significant (p>0.05).Postoperative Rhizoma Polygoni Cuspidati treatment group QTcd is also significantly less than ischemia group (p<0.05).The treatment of prompting Rhizoma Polygoni Cuspidati can obviously shorten QTcd interval.
Table 1 polygonin is on the impact (x ± s, ms) of mouse cardiac muscle ischemia preoperative and postoperative QT dispersion
| Group | Preoperative | Postoperative (7 days) |
| Sham operated rats | 36.3±3.5 | 37.5±3.8 |
| Ischemic infarction group | 35.3±3.6 | 64.1±7.5 *# |
| Polygonin treatment group | 36.5±3.5 | 40.3±5.5 |
Note: * p<0.05vs ischemic infarction group is preoperative, #p<0.05vs sham operated rats is postoperative and polygonin treatment group is postoperative
2.2 postoperative 7 days of ultrasonic cardiac function results displays, dead 4 of 40 heart infarction ischemia models, survival rate is 90%.Through preoperative and postoperative 7th day ultrasound Evaluation, heart infarction ischemia model group mouse core function obviously declines, and Fractional shortening drops to 25.43% ± 4.26 (P<0.05) by preoperative 53.11% ± 5.87; Left Ventricular Ejection Fraction drops to 35.64% ± 6.12 (P<0.05) by preoperative 75.43% ± 11; Ventricle obviously expands, left room end-diastolic diameter is extended to (3.57 ± 0.44) mm (P<0.05) by (2.84 ± 0.13) mm, shrinks last diameter and is extended to (2.33 ± 0.36) mm (P<0.05) by (1.61 ± 0.12) mm.Compared to ischemia heart infarction group, polygonin obviously improves left ventricular cardiac function (left room Fractional shortening postoperative 49.21% ± 6.11vs ischemia heart infarction group postoperative 25.43% ± 4.26, p<0.05; Left Ventricular Ejection Fraction postoperative 63.12% ± 7.23vs ischemia heart infarction group postoperative 35.64% ± 6.12, p<0.05; ), meanwhile, left room end-diastolic diameter and end-systole diameter all have improvement in various degree (seeing the following form 2).
Table 2 polygonin is on the impact (x ± s) of mouse cardiac muscle ischemia preoperative and postoperative function aroused in interest
Note: * p<0.05vs ischemic infarction group is preoperative, #p<0.05vs sham operated rats is postoperative and polygonin treatment group is postoperative
2.3 Ito
Report, during myocardial ischemia, Ito electric current density significantly reduces.Table 3 shows the Ito electric current density of sham operated rats, ischemic infarction group and polygonin treatment group.Result shows, three groups of preoperative Ito electric current densities are compared does not have significant difference (P=0.234).And the postoperative Ito electric current density of ischemic infarction group is significantly lower than sham operated rats.When+60mV, the preoperative Ito electric current density of sham operated rats, ischemic infarction group and polygonin treatment group is respectively (10.3 ± 1.5) pA/pF (n=24), (10.5 ± 1.6) pA/pF (n=25), (10.2 ± 1.9) pA/pF (n=29, P=0.14vs sham operated rats).And the Ito electric current density that during+60mV, sham operated rats, ischemic infarction group and polygonin treatment group are postoperative is respectively (9.8 ± 1.0) pA/pF (n=36), (5.8 ± 0.5) pA/pF (n=33, P<0.05vs sham operated rats), (8.7 ± 0.9) pA/pF (n=33, P<0.05vs ischemic infarction group).Result shows, and can significantly increase Ito electric current density after giving polygonin.
Table 3 polygonin is to mouse cardiac muscle ischemia preoperative and postoperative Ito current detecting (+60mV)
| Group | Preoperative (pA/pF) | Postoperative (7 days) (pA/pF) |
| Sham operated rats | 10.3±1.5 | 9.8±1.0 |
| Ischemic infarction group | 10.5±1.6 | 5.8±0.5 *# |
| Polygonin treatment group | 10.2±1.9 | 8.7±0.9 |
Note: * p<0.05vs ischemic infarction group is preoperative, #p<0.05vs sham operated rats is postoperative and polygonin treatment group is postoperative
2.4AP
As shown 4-6 display, the AP of sham operated rats, ischemic infarction group and polygonin treatment group.Preoperative and the postoperative AP multipole 20% (APD to three groups
20), APD multipole 50% (APD
50) and multipole 90% (APD
90) time-histories carry out statistical analysis, three groups of preoperative APD
20, APD
50and APD
90relatively there is no significant difference (P=0.231).The postoperative APD of sham operated rats
20, APD
50and APD
90be respectively (3.8 ± 0.3) ms, (9.1 ± 0.9) ms and (30.6 ± 3.2) ms (n=24), the postoperative APD of ischemic infarction group
20, APD
50and APD
90comparatively sham operated rats significant prolongation, be respectively (5.1 ± 0.3) ms (P=0.00vs sham operated rats), (14.4 ± 1.2) ms (P=0.00vs sham operated rats) and (49.6 ± 5.1) ms (P=0.01vs sham operated rats), n=45.And the postoperative APD of polygonin treatment group
20, APD
50and APD
90comparatively ischemic infarction group significantly shortens, be respectively (4.4 ± 0.5) ms (P<0.05vs ischemic infarction group), (10.6 ± 1.0) ms (P<0.05vs ischemic infarction group) and (36.5 ± 3.8) ms (P<0.05vs ischemic infarction group), n=32.And the resting membrane electric potential of three groups (RMP) is respectively (-78.9 ± 0.9) mV, (-79.1 ± 0.8) mV and (-78.5 ± 0.7) mV, three groups relatively do not have remarkable significant difference, P=0.334.Result shows, and can significantly shorten AP time-histories after giving polygonin.
Table 4 polygonin detects mouse cardiac muscle ischemia preoperative and postoperative AP20
| Group | Preoperative | Postoperative (7 days) |
| Sham operated rats | 3.5±0.5 | 3.8±0.3 |
| Ischemic infarction group | 3.3±0.3 | 5.1±0.3 *# |
| Polygonin treatment group | 3.7±0.4 | 4.4±0.5 |
Note: * p<0.05vs ischemic infarction group is preoperative, #p<0.05vs sham operated rats is postoperative and polygonin treatment group is postoperative
Table 5 polygonin detects mouse cardiac muscle ischemia preoperative and postoperative AP50
| Group | Preoperative | Postoperative (7 days) |
| Sham operated rats | 8.8±0.8 | 9.1±0.9 |
| Ischemic infarction group | 9.2±0.7 | 14.4±1.2 *# |
| Polygonin treatment group | 8.6±0.7 | 10.6±1.0 |
Note: * p<0.05vs ischemic infarction group is preoperative, #p<0.05vs sham operated rats is postoperative and polygonin treatment group is postoperative
Table 6 polygonin detects mouse cardiac muscle ischemia preoperative and postoperative AP90
| Group | Preoperative | Postoperative (7 days) |
| Sham operated rats | 29.7±2.3 | 30.6±3.2 |
| Ischemic infarction group | 30.1±2.1 | 49.6±5.1 *# |
| Polygonin treatment group | 28.5±2.4 | 36.5±3.8 |
Note: * p<0.05vs ischemic infarction group is preoperative, #p<0.05vs sham operated rats is postoperative and polygonin treatment group is postoperative
2.5 Ito subunit Kv4.2 and Kchip express
As shown in Figure 1, within 7 days, extract cardiac muscular tissue's albumen afterwards, western blotting detects the protein expression of Ito subunit Kv4.2 and Kchip.The myocardial cell infarction that ischemia causes, significantly can reduce the expression of Ito protein subunit, but what is interesting is, polygonin is treated, and significantly can improve the minimizing of this expressing quantity, increases Kv4.2 and Kchip protein content.
4. discuss
As everyone knows, voltage gated potassium channels (KV) plays an important role in the formation of Single Cardiac Cell (AP) repolarization, and AP repolarization extends and causes LQT syndrome.After acute myocardial infarction, there is obvious inhomogeneity in the electrophysiological characteristics between infarcted region and non-infarcted region, ventricle myoelectricity asynchronism is obviously increased, more easily formation is turned back, and (fourth surpasses, Chinese Journal of Pathophysiology, 004, 20:1472-1475) (fourth surpasses, China's cardiac pacing and cardiac electrophysiology magazine, 2003, 17:134-137), ventricular repolarization heterogeneity can use QT QT dispersion (QT dispersion in addition, QTd) represent, QTd reflects electrocardiogram and respectively to lead the degree of variation of QT interval, energy reflecting myocardium Repolarization time difference, prediction arrhythmia and good index (the Hii JT evaluating prognosis, Circulation, 1992, 86:1376).Because electrocardio is unstable after acute myocardial infarction, very easily cause malignant arrhythmia and sudden cardiac death.For the Focal point and difficult point that arrhythmia after acute myocardial infarction and sudden cardiac death are clinical positions always, although current antiarrhythmic drug is a lot, how to select with strong points, side effect is little, the medicine of highly effective and safe is still still unsolved clinical problem.For after myocardial infarction arrhythmia prevention research with and subsequent several clinical trials all fail, impel clinicist to recognize further, select importance and the urgency of rational antiarrhythmic drug.
Experimental result shows, after acute myocardial infarction, QTcd obviously increases, be easy to bring out the fatal arrhythmia such as ventricular tachycardia, ventricular fibrillation, and polygonin treatment obviously can shorten QTcd, improve room to quiver territory, thus can ecg stability be increased, that reduces the fatal arrhythmia such as ventricular tachycardia, ventricular fibrillation easily sends out tendency.Simultaneously, experimental result display Kv4.2 albumen raises, and the α subunit (Kv4.2) that the treatment of prompting polygonin significantly can increase ventricular repolarization ion channel Ito is expressed, and Ito electric current density is raised, by shortening Single Cardiac Cell, improve cardiac function.Polygonin treatment can obviously promote left room LVFS and Left Ventricular Ejection Fraction.In experimentation, do not find the arrhythogenic ill effect of other antiarrhythmic drugs of polygonin temporarily, show the effect of its uniqueness at control myocardial infarction arrhythmia.
Claims (9)
1. polygonin is preparing the purposes in arrhythmia product.
2. purposes as claimed in claim 1, it is characterized in that, described arrhythmia is caused by myocardial infarction.
3. polygonin suppresses the purposes in long Q-T interval syndrome product in preparation.
4. purposes as claimed in claim 3, it is characterized in that, described long Q-T interval, is caused by myocardial infarction.
5. polygonin is expressing the purposes in product for the preparation of increase Ito channel protein.
6. purposes as claimed in claim 5, is characterized in that, described Ito channel protein is one or more in Kv4.2 and Kchip.
7. purposes as described in one of claim 1-6, is characterized in that, described product comprises the one in medicine, reagent or food.
8. purposes as described in one of claim 1-6, is characterized in that, its occupation mode comprise be used alone or with other chemical substance conbined usage.
9. purposes as described in one of claim 1-6, is characterized in that, its working concentration is 20mg/kg.
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| CN113533563A (en) * | 2021-07-07 | 2021-10-22 | 健民药业集团股份有限公司 | Method for simultaneously detecting contents of four components of liver-soothing, stomach-harmonizing and pain-relieving traditional Chinese medicine |
| CN113533563B (en) * | 2021-07-07 | 2022-09-13 | 健民药业集团股份有限公司 | Method for simultaneously detecting contents of four components of liver-soothing, stomach-harmonizing and pain-relieving traditional Chinese medicine |
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