CN103989701B - Macrogol 4000 or polyethylene glycol 6000 application in preparation prevention or treatment cardiotoxicity of physaliatoxin medicine - Google Patents
Macrogol 4000 or polyethylene glycol 6000 application in preparation prevention or treatment cardiotoxicity of physaliatoxin medicine Download PDFInfo
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Abstract
The present invention relates to pharmaceutical technology field, it is specifically related to the application in preparation prevention or treatment cardiotoxicity of physaliatoxin medicine of Macrogol 4000 or polyethylene glycol 6000, to solve what shortage at present can be applied clinically, the medicine of prevention or treatment cardiotoxicity of physaliatoxin, stings the increasing harm brought to people's life reducing Jellyfish. Invention broadly provides the application in preparation prevention or treatment cardiotoxicity of physaliatoxin medicine of Macrogol 4000 or polyethylene glycol 6000. Macrogol 4000 or polyethylene glycol 6000 can the myocardial cell calcium ion overload of effective antagonism medusocongestin induction, thus the cytotoxic effect of effectively antagonism medusocongestin induction, decrease Jellyfish and sting the death caused, filled up at present clinically not for preventing or treat the blank of cardiotoxicity of physaliatoxin medicine.
Description
Technical field
The present invention relates to pharmaceutical technology field, be specifically related to the application in preparation prevention or treatment cardiotoxicity of physaliatoxin medicine of Macrogol 4000 or polyethylene glycol 6000.
Background technology
Jellyfish is that a class is low to be waited without vertebra zooplankton, belongs to Cnidaria (also known as Coelenterata), Scyphozoa. In recent years, owing to the many factors such as global warming, sea water eutrophication, Fish overfishing cause marine eco-environment severe exacerbation, global many marine sites Jellyfish abnormality proliferation, population outbreak. In fact, Jellyfish is also that the mankind injure one of maximum marine animal, it is modal injuries from marine creature (Dong that Jellyfish stings, Z., etal., JellyfishbloomsinChina:Dominantspecies, causesandconsequences [J] .MarPollutBull, 2010.60 (7): 954-63; Al-Rubiay, K., etal., SkinandsystemicmanifestationsofjellyfishstingsinIraqifis hermen [J] .LibyanJMed, 2009.4 (2): 75-7.), the whole world there are about 1.5 hundred million seawater bath fans every year and fisherman is perplexed by Jellyfish deeply, and Fla. about 200,000 people every year stung by Jellyfish, Australia also has about tens of thousands of people to be stung by Jellyfish every year, and wherein lethal case is also not uncommon for. China there is not yet the complete epidemiologic data stung about Jellyfish, but since nineteen eighty-three, has the clinical disease number of cases of bibliographical information more than 2000 examples (including 13 example deaths), and is the report of last decade mostly, presents growth trend year by year. Jellyfish stings patient and may occur in which the local symptoms such as severe pain, inflammation and necrosis, severe patient it may also occur that muscle spasm, even dead (the Burnett of breathing, cyclic inhibition, J.W., Medicalaspectsofjellyfishenvenomation:pathogenesis, casereportingandtherapy [J] .Hydrobiologia, 2001.451:1-9.).
It is owing to nematocyst densely covered on its tentacle is launched caused by ecthoaeum release toxin that Jellyfish stings, medusocongestin is the Peptide toxin that a class formation is novel, toxicity is extremely strong, there is the multiple biological activity (XiaoL. such as cutaneous necrosis, cardiovascular, haemolysis, nerve, Liver and kidney, heart, etal.Theacutetoxicityandhematologicalcharacterizationoft heeffectsoftentacle-onlyextractfromthejellyfishCyaneacap illata [J] .MarDrugs, 2011,9:526-534; XiaoL., etal.Invitroandinvivohaemolyticstudiesoftentacle-onlyext ractfromjellyfishCyaneacapillata [J] .ToxicolInVitro, 2010,24:1203-1207.). Wherein, the Jellyfish that the acute circulatory failure that the cardiac toxicity of medusocongestin causes is well recognized as stings lethal main cause.
Although there being document to show, the mechanism of action of cardiotoxicity of physaliatoxin is likely to relevant with myocardial cell calcium overload, but not specific cationic channel blocker (LaCl3) can effectively suppress myocardial cell calcium overload (Bailey, P.M., etal., AfunctionalcomparisonofthevenomofthreeAustralianjellyfis h Chironexfleckeri, Chiropsalmussp., andCarybdeaxaymacana oncytosolicCa2+, haemolysisandArtemiasp.lethality [J] .Toxicon, 2005.45 (2): 233-242.), but owing to other ion streams are also had impact by the Tricationic in these blocker, as blocked ICaIAnd ICaTAnd IKr, and can not apply under physiological conditions, which limits they application clinically. Therefore, up to now, the mechanism of action of cardiotoxicity of physaliatoxin not yet illustrates, and the medicine of prevention or treatment cardiotoxicity of physaliatoxin also has no research successfully report.
Polyethylene Glycol (English name: Polyethyleneglycol), chemical formula: HO (CH2CH2O) n, chemical structural formula is as follows:
Polyethylene Glycol is the inorganic hydrophilic polymer that a class is nontoxic, non-stimulated, and at present, the degree of polymerization of commercially available Polyethylene Glycol mainly has 200,300,400,600,800,1000,1500,2000,3000,4000,6000,8000. Polyethylene Glycol can be injected directly into blood, uses safety. Its main effect is effectively to repair the cell membrane damage that various factors causes, thus stoping intraor extracellular ion imbalances, it is prevented that cell death. In Traumatic brain injury and spinal trauma disease model, Polyethylene Glycol has notable therapeutic effect, demonstrate applications well prospect (Borgens, R.B., etal., Understandingsecondaryinjury [J] .QRevBiol, 2012.87 (2): 89-127.).
But up to now, have no about Polyethylene Glycol for preventing or treat the relevant report of cardiotoxicity of physaliatoxin.
Comprehensive document above analysis, is badly in need of at present a kind of can applying clinically, the medicine of prevention or treatment cardiotoxicity of physaliatoxin, stings the increasing harm brought to people's life reducing Jellyfish.
Summary of the invention
In order to solve to lack clinically at present the medicine of effectively prevention or treatment cardiotoxicity of physaliatoxin, the invention provides the new application of a kind of Macrogol 4000 or polyethylene glycol 6000.
The invention provides the application in preparation prevention or treatment cardiotoxicity of physaliatoxin medicine of Macrogol 4000 or polyethylene glycol 6000.
The present invention is through test display, and Macrogol 4000 or polyethylene glycol 6000 can extrinsic AGB stars path cardiac myocyte Ca that effectively antagonism medusocongestin causes2+Rising. In isolated heart is tested, Macrogol 4000 or 6000 effectively suppresses the core function abnormality that medusocongestin causes. On mice or rat poisoning model, intravenous injection Macrogol 4000 or 6000 can significantly improve animal survival rate, improves the core function abnormality that medusocongestin causes simultaneously.
Macrogol 4000 of the present invention or polyethylene glycol 6000 application in preparation prevention or treatment cardiotoxicity of physaliatoxin medicine, the dosage form of described medicine is injection. Dosage is generally 100��150mg/ kg body weight/sky, specifically can be changed according to individual age, the state of an illness etc.
The inventors discovered that Cyanea capillata (Cyaneacapillata, C.capillata) thick poison extracting solution (tentacleextract, TE) may result in laboratory animal heart tissue Ca2+Content is abnormal to be increased and myocardial cell cytoplasm calcium concentration ([Ca2+]i) abnormal rising (i.e. calcium overload), it was shown that medusocongestin is the normal physiological function being affected heart by inducing cardiomyocytes calcium overload.
Additionally, the present inventor adopts the method for pharmaceutical intervention to myocardial cell Ca2+The approach raised is studied, found that: TE can activate extrinsic AGB stars path, also can activate interior calcium release path.
Discharging in path at interior calcium, RyR inhibitor Ryanodine (20 ��Ms) can significantly inhibit the TE endochylema [Ca brought out2+]iRaise, but PKA inhibitor H89 (10 ��Ms) can not suppress the TE endochylema [Ca brought out2+]iRaise, illustrate that TE activates interior calcium not by cAMP/PKA/RyR signal path and discharges path, and be probably direct (toxic components enters endochylema and directly activates RyR path) or cause interior calcium to discharge by other approach (calcium such as calcium induction discharges path etc.) activation RyR. But, owing to skeletal muscle and cardiac muscular tissue are all had obvious paralysis effect by RyR inhibitor Ryanodine, therefore it is not used to the drug development of humans and animals.
In extrinsic AGB stars path, L-type calcium channel blocker (includes verapamil, nifedipine, diltiazem) does not have antagonistic effect; Non-specific cationic channel blocker LaCl3[the Ca of (100 ��Ms) energy partial agonist TE induction2+]iRaise; The calcium that TE is brought out by film sealing agent Polyethylene Glycol (25mM) raises extremely strong inhibition, but it is closely relevant with its molecular size range: polyethylene glycol 200-1000 is nearly unavailable, Macrogol 2000 part is effective, Macrogol 4000 or 6000 suppresses the TE calcium caused to raise completely, PEG 8000 is bad due to dissolubility, and the inhibition that the TE calcium caused is raised is not good yet. It is therefore believed that TE has no effect on existing L-type calcium channel on myocardial cell membrane, containing PFP in the toxin component of TE, the latter quickly can form duct on cell membrane, causes the outer Ca of born of the same parents2+Interior stream, ultimately results in the duct that myocardial cell calcium overload, Macrogol 4000 or polyethylene glycol 6000 can effectively be formed on repair cell the film, [Ca that antagonism TE causes2+]iRaise.
Macrogol 4000 of the present invention is the degree of polymerization is the Polyethylene Glycol of 4000.
Polyethylene glycol 6000 of the present invention is the degree of polymerization is the Polyethylene Glycol of 6000.
Macrogol 4000 of the present invention or polyethylene glycol 6000 application in preparation prevention or treatment cardiotoxicity of physaliatoxin medicine, Jellyfish therein is Cyanea capillata.
Macrogol 4000 of the present invention or polyethylene glycol 6000 application in preparation prevention or treatment cardiotoxicity of physaliatoxin medicine, prevention therein or treatment cardiotoxicity of physaliatoxin medicine are for improving the core function abnormality that medusocongestin causes.
Macrogol 4000 of the present invention or polyethylene glycol 6000 application in preparation prevention or treatment cardiotoxicity of physaliatoxin medicine, prevention therein or treatment cardiotoxicity of physaliatoxin medicine are for improving the acute circulatory failure that medusocongestin causes.
The invention provides the application in preparation prevention or treatment cardiotoxicity of physaliatoxin medicine of Macrogol 4000 or polyethylene glycol 6000, Macrogol 4000 or polyethylene glycol 6000 can the myocardial cell calcium ion overload of effective antagonism medusocongestin induction, thus the cytotoxic effect of effectively antagonism medusocongestin induction, decrease Jellyfish and sting the death caused, filled up at present clinically not for preventing or treat the blank of cardiotoxicity of physaliatoxin medicine.
Accompanying drawing explanation
Fig. 1 is H9c2 cellular level, the calcium overload calcium ion concentration change of blank group Cyanea capillata toxin-induced, and wherein, A is calcium fluoroscopic image (40 times); B is calcium ion concentration time variation diagram;
Fig. 2 is H9c2 cellular level, the calcium overload calcium ion concentration change of PEG200 (25mM) antagonism Cyanea capillata toxin-induced, and wherein, A is calcium fluoroscopic image (40 times); B is calcium ion concentration time variation diagram;
Fig. 3 is H9c2 cellular level, the calcium overload calcium ion concentration change of PEG600 (25mM) antagonism Cyanea capillata toxin-induced, and wherein, A is calcium fluoroscopic image (40 times); B is calcium ion concentration time variation diagram;
Fig. 4 is H9c2 cellular level, the calcium overload calcium ion concentration change of PEG1000 (25mM) antagonism Cyanea capillata toxin-induced, and wherein, A is calcium fluoroscopic image (40 times); B is calcium ion concentration time variation diagram;
Fig. 5 is H9c2 cellular level, the calcium overload calcium ion concentration change of PEG2000 (25mM) antagonism Cyanea capillata toxin-induced, and wherein, A is calcium fluoroscopic image (40 times); B is calcium ion concentration time variation diagram;
Fig. 6 is H9c2 cellular level, the calcium overload calcium ion concentration change of PEG4000 (25mM) antagonism Cyanea capillata toxin-induced, and wherein, A is calcium fluoroscopic image (40 times); B is calcium ion concentration time variation diagram;
Fig. 7 is H9c2 cellular level, the calcium overload calcium ion concentration change of PEG6000 (25mM) antagonism Cyanea capillata toxin-induced, and wherein, A is calcium fluoroscopic image (40 times); B is calcium ion concentration time variation diagram;
Fig. 8 is H9c2 cellular level, the cytotoxic effect of PEG4000/6000 (10mM) antagonism Cyanea capillata toxin-induced;
Fig. 9 is isolated heart level, PEG4000/6000 (25 ��Ms) antagonism Cyanea capillata toxin cardiac toxicity effect;
Wherein, A is changes in heart rate;
B is coronary flow change;
C is the left chamber pressure maximum rate of change of rising;
D is the left chamber pressure maximum rate of change of decline;
E is left ventricular developed pressure change;
F is left ventricular end diastolic presssure change;
Figure 10 is whole animal level, the death of mice rate change of PEG4000/6000 (25mM) antagonism Cyanea capillata toxin-induced;
Figure 11 is whole animal level, and the Cardiac Function in Rat of PEG4000/6000 (25mM) antagonism Cyanea capillata toxin-induced is abnormal;
Wherein, A is changes in heart rate;
B is mean arterial pressure change;
C is the left chamber pressure maximum rate of change of rising;
D is the left chamber pressure maximum rate of change of decline;
E is left ventricular developed pressure change;
F is left ventricular end diastolic presssure change.
Detailed description of the invention
Below in conjunction with embodiments of the invention and accompanying drawing, the enforcement of the present invention is elaborated; following example are to be carried out under premised on technical solution of the present invention; give detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment.
Cyanea capillata C.capillata used by following example picks up from Zhejiang Province's nutrients in August, 2012, identify through Aquatic Products Inst. Attached to Jimei Univ. professor Hong Huixin, belong to Cnidaria (also known as Coelenterata), Scyphozoa, rosy clouds Medusa.
PEG200-6000 used by following example is purchased from Sheng Gong biotech firm, it is possible to purchased from Tianjin Tiancheng Pharmaceutical Co., Ltd. etc.
Embodiment 1. prepares Jellyfish slightly poison extracting solution
Cyanea capillata C.capillata picks up from Zhejiang Province's nutrients in August, 2012, cuts rapidly its tentacle, immediately that tentacle dry ice is freezing, transports that to be placed on-70 DEG C of ultra cold storage freezers frozen standby back. During preparation TE, weigh appropriate tentacle sample, add equal-volume autogamy 3.34% sea water (NaCl28g, MgCl2��6H2O5g, KCl0.8g, CaCl21.033g, adds water and is settled to 1L) in 4 DEG C of self-dissolvings 4 days, magnetic stirring apparatus stirred 2 times every day, 30min/ time. With 100 order cell screen filtration 3 times, centrifugal 3 times of filtrate 10000 �� g, 15min/ time, aforesaid operations all carries out in ice bath. Supernatant collected after centrifugal is TE, after detection TE protein concentration (Bradford method), with 50ml centrifuge tube subpackage, and in-70 DEG C of frozen samples. Use 4 DEG C of dialysed overnight of PBS solution before using TE every time.
Embodiment 2. is in myocardial cell, isolated heart and three aspects of whole animal, and PEG4000/6000 antagonism cardiotoxicity of physaliatoxin is tested
Experiment PEG200-6000 is purchased from Sheng Gong biotech firm, and wherein PEG200 and PEG600 is colourless transparent liquid, and PEG1000 is white waxy solid, and PEG2000,4000,6000 are white solid.
2.1 in myocardial cell level, and PEG4000/6000 can the cell calcium overload of obvious antagonism medusocongestin induction
Rat myocardial cell strain (H9c2, numbering: 1307) is purchased from Chinese Academy of Sciences's cell bank. Complete culture solution is that condition of culture is 37 DEG C, 5%CO containing 10% hyclone, 100U/mL penicillin, the DMEM high glucose medium of 100 �� g/mL streptomycins2, relative humidity 95%. Microscopic observation, when Growth of Cells to about 80%, with 0.25% trypsin containing 0.02%EDTA) peptic cell, carry out passage. Within every 2-3 days, change a culture fluid.
Cultivating H9c2 more than cell 48h in copolymerization Jiao's ware, under light microscopic, observation of cell density starts experiment when reaching 80%. After 10 ��m of ol/L application liquid addition culture dish lucifuges of Fluo-4/AM (buying from American I nvitrogen company) are hatched 30-40min, with without calcium Hepes liquid (160.8mMNaCl, 3.15mMKCl, 0.7mMNa2HPO4.12H2O, 33mMHEPES, pH7.65) clean 3 times, to remove unsupported free Fluo-4/AM background. Experiment is divided into: TE group, PEG200-6000 pharmaceutical intervention group. Specifically refer to, culture dish is separately added into calcic Hepes liquid (160.8mMNaCl, 3.15mMKCl, 0.7mMNa2HPO4.12H2O, 33mMHEPES, 0.075%CaCl.2H2O, pH7.65) and each 200 �� l of calcic Hepes liquid (containing PEG200-6000,25mM), put into 37 DEG C of incubators and hatch, be placed on the object stage of Laser Scanning Confocal Microscope after 15min to be checked.Arranging parameter: 1. excitation wavelength is 488nm, transmitting wavelength is 526nm, scans 1 time every 10s, continuously scanning 50; 2. scan mode: xyt (time series scanning); 3. scanning density: 512 �� 512; 4. object lens multiple: 40 times. After setting above-mentioned parameter, adjustment focal plane makes fluoroscopic image the most clear, and selected cell starts record, gathers image, after the 5th image taking terminates, and addition TE (20 �� g/mL), Ca in cell after Continuous Observation TE addition2+The dynamic change of fluorescence. Calculate [Ca2+]iFluorescence intensity increases percent (%)=(Fmax-F0)/F0�� 100%, wherein FmaxIt is each group peak value [Ca after adding TE2+]iFluorescence intensity, F0It is [Ca before addition TE2+]iFluorescence tranquillization intensity.
Relatively PEG200-6000 is to the TE [Ca induced2+]iThe impact raised, judges whether PEG has protection cell membrane, it is suppressed that the effect of myocardial cell calcium overload. Result is as shown in figs. 1-7, find that PEG200-1000 is nearly unavailable to the TE calcium overload induced, PEG2000 part is effectively, PEG4000/6000 can suppress the TE calcium overload induced completely, prompting PEG4000/6000 can effectively suppress the calcium overload that medusocongestin is induced, and has the effect of obvious antagonism cardiac toxicity.
2.2 in myocardial cell level, and PEG4000/6000 can obvious antagonism medusocongestin myocardiocyte toxicity
H9c2 cell viability adopts mtt assay to measure, experiment point TE group, PEG4000/6000 pharmaceutical intervention group (often organizing n=6). Wherein in TE group, control wells adds the equal-volume culture fluid without TE, toxin hole adds the TE (2.5-100 �� g/ml) of variable concentrations; In PEG4000/6000 pharmaceutical intervention group, medicine internal reference hole gives PEG4000/6000 (10mM) respectively and hatches, but is added without TE; Pharmaceutical intervention hole gives PEG4000/6000 (10mM) and hatches, and adds the TE (2.5-100 �� g/ml) of variable concentrations after 15min. After being disposed, 96 orifice plates are put into incubator continue to hatch 2h, then every hole adds 20 �� lMTT solution (5mg/mL), shaking up gently, after continuing cultivation 4h, exhaust culture fluid, every hole adds 200 �� lDMSO solution, room temperature jog 30min, after purple crystal is completely dissolved, with detecting each group of absorbance (OD value) under microplate reader 490nm wavelength. TE group cell survival rate (%)=TE concentration group OD value/matched group OD value �� 100%. PEG group cell survival rate (%)=PEG intervention group OD value/PEG internal reference group OD value �� 100%
Relatively PEG4000/6000 group cell survival rate and corresponding TE group cell survival rate, thus judging whether PEG4000/6000 has antagonism medusocongestin cytotoxic effect in myocardial cell level. As shown in Figure 8, display PEG4000/6000 all can significantly improve the survival rate of the myocardial cell processed through medusocongestin to result, illustrates in myocardial cell level, and PEG4000/6000 has the effect of obvious antagonism myocardiocyte toxicity.
2.3 in isolated heart level, and PEG4000/6000 can antagonism cardiotoxicity of physaliatoxin
Male SD rat 24 (is bought from Second Military Medical University, PLA's Experimental Animal Center), body weight 300 �� 20g, after urethane (buying from chemical reagents corporation of traditional Chinese medicines group) the 1.2g/kg intraperitoneal anesthesia containing heparin (400IU/kg), open rapidly breast to core, it is placed in the Krebs-Henseleit (KH of 4 DEG C of pre-coolings, mmol/L:NaCl118, KCl4.7, MgSO41.2, NaHCO325, KH2PO41.2, CaCl22.5, glucose 11.0, pH7.35-7.45) solution stops fighting.According to classical Langendorff method, aorta is fixed on perfusion device cannula fixation one intubate on, open three-way valve, connect 37 DEG C of KH perfusates preheated, make recovering beat of heart. Perfusate is in advance with 95%O2With 5%CO2Fully saturated, perfusion pressure maintains 60-80mmHg. After cardiac perfusion is stable, cut left auricle, insert sacculus through otch to left ventricle, and connect bio signal analysis system (MPA-2000, Alcott, Shanghai) by pressure transducer. Then it is slowly injected into water to sacculus, makes intracapsular pressure maintain 2-8mmHg.
In experimentation, the parameters of left ventricular function such as (LVDP), Left ventricular end diastolic pressure (LVEDP) and coronary flow (CF) are pressed in omnidistance recorded heart rate (HR), maximal ascending rate of internal pressure of left ventricle (dP/dtmax), maximal descending rate of internal (dP/dtmin), left ventricle development.
24 SD rats are randomly divided into matched group (normal saline+normal saline), poisoning group of TE (normal saline+TE) and PEG4000/6000 pharmaceutical intervention group (PEG4000/6000+TE) totally 4 groups, often organize each 6. Wherein PEG is by KH perfusion administration (25 ��Ms), and TE is by side pipe administration (0.18mg), to the change of each parameters of left ventricular function of observation post administration isolated heart. Result, as it is shown in figure 9, the parameters of left ventricular function such as HR, CF, dP/dt and LVDP of display PEG4000/6000 pharmaceutical intervention group is significantly better than that TE group, illustrates in isolated heart level, and PEG4000/6000 has the effect of obvious antagonism cardiotoxicity of physaliatoxin.
2.4 in whole animal level, and PEG can the death of mice of antagonism medusocongestin induction
Kunming mice (buying from Second Military Medical University, PLA's Experimental Animal Center) is randomly divided into Normal group (normal saline+normal saline), negative treatment group (TE+ normal saline), PEG4000/6000 treatment group (TE+PEG4000/6000), often organizes each 10. Wherein, treatment group first gives tail vein injection TE (8.4mg/kg), immediately after injecting normal saline or PEG; Normal group gives twice isopyknic physiological saline, to observation post administration and record the death condition of mice in 48h. As shown in Figure 10, PEG4000/6000 substantially reduces the mortality in acute phase of TE induction to result, compares TE group (in 2h, mice is all dead), and after PEG4000 injection, 2h mice all survives, and after 48h, survival rate is 20%; After PEG6000 injection, 2h mouse survival rate is 80%, and after 48h, survival rate is 50%, illustrates that PEG4000/6000 can substantially reduce the acute poisoning death of TE induction.
2.5 in whole animal level, and PEG can the Cardiac Function in Rat Indexes Abnormality of antagonism medusocongestin induction
Male SD rat (buys from Second Military Medical University, PLA's Experimental Animal Center) 24, body weight 200 �� 20g, it is randomly divided into Normal group (normal saline+normal saline), negative treatment group (TE+ normal saline), PEG4000/6000 treatment group (TE+PEG4000/6000) totally 4 groups, often organizes each 6. 25% urethane is fixing after (buying from chemical reagents corporation of traditional Chinese medicines group) 1.2g/kg intraperitoneal anesthesia, venous cannulation of taking action. Wherein, left femoral artery intubates Bonding pressure sensor, and bio signal is analyzed system (MPA-2000, Alcott, Shanghai) and monitored and record the change of mean arterial pressure (MAP). Right carotid intubates to left ventricle, monitors following parameters of left ventricular function: HR, dP/dtmax, dP/dtmin, LVDP and LVEDP.Right side external jugular vein intubates for intravenously administrable, and wherein, treatment group first gives TE (2.4mg/kg), gives normal saline or PEG4000/6000 respectively as negative treatment group and PEG4000/6000 treatment group after 1min; Normal group gives twice isopyknic physiological saline.
As shown in figure 11, display PEG4000/6000 substantially alleviates parameters of left ventricular function (HR, the MAP of TE induction to result, dP/dtmax, dP/dtmin, LVDP) decline, illustrating in whole animal level, PEG4000/6000 can the cardiac toxicity of obvious antagonism medusocongestin.
Above-described embodiment is the present invention preferably embodiment, but embodiments of the present invention are not restricted to the described embodiments. The deformation made under other any spirit without departing from the present invention and principle, is all considered as protection scope of the present invention.
Claims (5)
1. Macrogol 4000 or polyethylene glycol 6000 application in preparation prevention or treatment cardiotoxicity of physaliatoxin medicine.
2. Macrogol 4000 as claimed in claim 1 or polyethylene glycol 6000 application in preparation prevention or treatment cardiotoxicity of physaliatoxin medicine, it is characterised in that described prevention or treatment cardiotoxicity of physaliatoxin medicine are injection.
3. Macrogol 4000 as claimed in claim 1 or polyethylene glycol 6000 application in preparation prevention or treatment cardiotoxicity of physaliatoxin medicine, it is characterised in that described Jellyfish is Cyanea capillata.
4. Macrogol 4000 as claimed in claim 1 or polyethylene glycol 6000 application in preparation prevention or treatment cardiotoxicity of physaliatoxin medicine, it is characterized in that, described prevention or treatment cardiotoxicity of physaliatoxin medicine are for improving the core function abnormality that medusocongestin causes.
5. Macrogol 4000 as claimed in claim 1 or polyethylene glycol 6000 application in preparation prevention or treatment cardiotoxicity of physaliatoxin medicine, it is characterized in that, described prevention or treatment cardiotoxicity of physaliatoxin medicine are for improving the acute circulatory failure that medusocongestin causes.
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