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Study On The Effect Of Carmichaelii Water-solubility Alkaloid On Heart Failure

Posted on:2016-07-22Degree:MasterType:Thesis
Country:ChinaCandidate:S HeFull Text:PDF
GTID:2334330482971353Subject:Pharmacology
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Objective:To studythe therapeutic effects of acontum fischeri mankshood water-solubility alkaloid on heart failure.Methods: ① Use propafenone hydrochloride to copy the model rats of AHF. After it, recording the HR and left ventricular pressure by BL-420 system. Then, Intravenous Inject acontum fischeri mankshood water-solubility alkaloid(0.025、 0.050、 0.10ml/kg, the content of extractive:0.05g/ml) or positive drugSheng Mai (参麦) Injection (6.67g/kg), Measuring the change of HR、+dp/dtmax and -dp/dtmax after administration 5,10,20,30,60min.Adopt the same method to deal with anther batch of rats, anddetermine the concentration ofAng-Ⅰ,Ang-Ⅱ,TNF-α, ANP, BNP, ALD by blood sampling at the time point of 20min by ELISA. ② Culture the myocardial cells, gotten from the neonatal rats, for 5 days until the cells becoming mature, then after usingNembutal (0.8%) to make the heart-failure cells model for 5min administrate them with 3 concentrations of acontum fischeri mankshood water-solubility alkaloid (0.01,0.02,0.04 g·L-1) and deslanoside injection (4mL·L-1), observe the morphological characteristics of the cells and record the changes by taking photos 90min later.Culture the myocardial cells, administrate in the same way, determine the vitality of the myocardial cells’ membrane ATP enzyme and the concentration of relative ions and cytokines 90min later. Then after usingNembutal (0.8%) to make the heart-failure cells model for 5min administrate them with 3 concentrations of acontum fischeri mankshood water-solubility alkaloid (0.01,0.02,0.04 g·L-1) and deslanoside injection (4mL·L-1), determine the vitality of the myocardial cells’membrane ATP enzyme, relative cytokines and the concentration of relative ions 90min later.Results:①Intravenous Injection ofacontum fischeri mankshood water-solubility alkaloid (0.025~0.10ml/kg) can increase the HR,+dp/dtmax and decrease the-dp/dtmax of the rats with acute heart failure. To some degree, it also can decrease the concentration of Ang-II,TNF-a, ANP, BNP, ALD, which were increased by modeling. ② To compare with the blank control group, the model group’smorphological characteristics of the cells were changed, the shape of the cells became more circular, and filiform antennas were developed, cell beat became weak or stopped. After administration, the cells of each drag groups were recovered in different degrees. To compare with the blank control group, the drug group’sliveness of cells rose,the concentrate of Na+, Ca2+ was decreased; On the contrary, the concentrate of K+and the activity of Na+-K+-ATP enzyme, Ca2+-ATP enzyme,Ca2+-Mg2+-ATP enzyme were increased.To compare with the model group, deslanoside injection (4mL · L-1) andacontum fischeri mankshood water-solubility alkaloid (1.25 X 10-3,2.50 X 1O-3,5.00 X 10’3g/kg) can increase the liveness of heart-failure cells model and the concentrate of Na+,Mg2+, and also can enhance the activity of Ca2+-ATP enzyme,Ca2+-Mg2+-ATP enzyme; Conversely, all the administrated groups have the effect that they can decrease K+, Ca2+in the myocardial cells and the contents of relative cytokines, and inhibit the activity of Na+-K+-ATP enzyme.Conclusions:Acontum fischeri mankshood water-solubility alkaloid has cardiac effect. The mechanism of it’s therapeutic effect may relate to adjusting the rennin-angiotensin-aldosterone system and adjusting the activity of ATP enzyme and the concentrate of relative ions and cytokines in myocardial cells.
Keywords/Search Tags:Acontum fischeri mankshood water-solubility alkaloid, heart failure model, myocardial cell, ions, ATP enzyme, cytokines
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