The Mechanism Study Of DAA-I And Xinmaitong On Rat With Heart Failure

Objective:Congestive heart failure(CHF)is the end stage of all kinds of heart diseases,and is also the main death cause among the patients of heart disease.The abnormality of myocardial contractile protein is one of the main reasons of myocardial systolic and diastolic functional decline.This experiment set CHF model with Doxoubicin,which can induce myocardial injury.The main purpose in this experiment is to observe the left ventricular function,the plasma concertraction of ANP and ALD,the content of Ventricular myosin light chains,the activity of Glutathione peroxidase and Na^+--K^+--ATPase ) in heart failure rat model and to explore the protective effects of myocardial systolic and diastolic function and the possible mechanisms of both Xinmaitong and DAA-Ⅰ.Methods:1.Manufacture of Animal Model:106 SPF SD Rats weighing from 220 to 250 gram were divided into seven groups by random digits table:(1)Normal contorl group;(2) Heart failure model group;(3) DAA-Ⅰgroup;(4) DAA-Ⅰ& Indomethacin group;(5) Indomethacin group;(6) Xinmaitong group;(7) DAA-Ⅰ& Xinmaitong group.Each group has 16 rats whereas the normol group has 10.We set all groups of HF model except the normal control group with Doxorubicin,which can induce myocardial injury.After the successful model setting,drug treatment is implemented according to the requirement of each group.2.Left ventricular function TestingLeft ventricular function Testing:Each model group is to be on Left ventricular function Testing on the 56th day.Specific methods are as follows:Incise the middle of the neck.Expose and blunt separate the left common carotid Artery. Inject Heparin into a catheter.Insert the catheter into the left Ventricle by the left common carotid Artery.Because the other end of the catheter is connected with a pressure sensor,so we can make relevant records to analysis the system through the acquisition of Biological signals.3.Indicators Detection:After the Cardiac function Testing,then check the corresponding materials in accordance with the above-mentioned indicators,including the content of Vmtricular myosin light chains(VMLC), the activity of Glutathione peroxidase and Na^+--K^+--ATPase and the detection of plasma ANP and ALD.Results:1.Left ventricular function Testing:Compared with normal control group,the heart failure model group showed that the left ventricular function had decreased,and the comparison had significant deviation in statistics. (p＜0.05).Compared with Heart failure model group,DAA-Ⅰgroup,DAA-Ⅰ& Xinmaitong group and Xinmaitong group showed that the left ventricular function had improved to different extents, and the comparison had significant deviation in statistics.(p＜0.05);DAA-Ⅰ& Indomethacin group,Indomethacin group show that the left ventricular function had not changed,and it had no statistical significance(p＞0.05).Among them,DAA-Ⅰ& Xinmaitong group is prior to DAA-Ⅰgroup,while DAA-Ⅰgroup is prior to Xinmaitong group,and the comparison had significant deviation in statistics.(p＜0.05).2.Plasma ANP Detection:The detection of plasma ANP(pg/ml) in rat model by Radioinmunoassay Method showed that:Compared with normal control group(122.00±17.739),the content of Plasma ANP in heart failure model group(265.00±47.422) had increased,and the comparison had significant deviation in statistics.(p＜0.05).Compared with Heart failure model group,DAA-Ⅰgroup (133.00±23.627),Indomethacin group(138.50±20.641),DAA-Ⅰ& Xinmaitong group (125.50±47.084) and Xinmaitong group(112.44±8.233) had decreased to different extents, and the comparison had significant deviation in statistics.(p＜0.05);DAA-Ⅰ& Indomethacin group(315.09±83.62) had increased,and the comparison had significant deviation in statistics.(p＜0.05).Among them,DAA-Ⅰgroup is higher than DAA-Ⅰ& Xinmaitong group,while DAA-Ⅰ& Xinmaitong group is higher than Xinmaitong group,and the comparison had significant deviation in statistics.(p＜0.05).3.Plasma ALD Detection:The detection of plasma ALD(pg/ml) in rat model by Radioinmunoassay Method showed that:Compared with normal control group(116.00±24.459),the content of Plasma ALD in heart failure model group(268.56±27.139)had increased,and the comparison had significant deviation in statistics.(p＜0.05).Compared with Heart failure model group,DAA-Ⅰgroup(87.64±19.765),DAA-Ⅰ& Xinmaitong group(115.00±23.324) and Xinmaitong group(116.29±7.296) had decreased to different extents,and the comparison had significant deviation in statistics.(p＜0.05);DAA-Ⅰ& Indomethacin group(1048.00±765.752) and Indomethacin group (293.91±53.810) had increased,and the comparison had significant deviation in statistics.(p＜0.05).Among them,DAA-Ⅰ& Xinmaitong group is the same as Xinmaitong group,while Xinmaitong group and DAA-Ⅰ& Xinmaitong group are higher than DAA-Ⅰgroup,and the comparison had significant deviation in statistics.(p＜0.05).4.Vrntricular myosin light chains(VMLC) Detection:The detection of vrntricular myosin light chains(ug/gprot)in rat model by Radioinmunoassay Method showed that:Compared with normal control group(35.433±6.913),the content of Vrntricular myosin light chains(VMLC)in heart failure model group(8.621±1.804) had decreased significant,and the comparison had significant deviation in statistics. (p＜0.05).Compared with heart failure model group,DAA-Ⅰgroup(18.203±5.445),DAA-Ⅰ& Xinmaitong group(28.898±9.948) and Xinmaitong group(13.573±2.108) had increased to different extents,and the comparison had significant deviation in statistics.(p＜0.05);DAA-Ⅰ& Indomethacin group(8.730±1.618),Indomethacin group(8.656±1.939) show had not changed, and it had no statistical significance(p＞0.05).Among them,DAA-Ⅰ& Xinmaitong group is higher than DAA-Ⅰgroup,while DAA-Ⅰgroup is higher than Xinmaitong group,and the comparison had significant deviation in statistics.(p＜0.05).5.Glutathione peroxidase Detection:The detection of the activity of Glutathione peroxidase(U/gprot) and in myocardial homogenate on rat models by Colorimetry indicated that:Compared with normal control group (3093.50±966.82),the activity of Glutathione peroxidase in Heart failure model group(2055.72±1547.74) had decreased,and the comparison had significant deviation in statistics.(p＜0.05).Compared with heart failure model group,DAA-Ⅰgroup(2840.51±2147.30),Indomethacin group(3177.96±1360.73),DAA-Ⅰ& Xinmaitong group(5385.37±4573.11) and Xinmaitong group(3235.62±1313.55) had increased to different extents,and the comparison had significant deviation in statistics.(p＜0.05);DAA-Ⅰ& Indomethacin group(1196.61±679.62) had decreased,and the comparison had significant deviation in statistics.(p＜0.05).Among them, DAA-Ⅰ& Xinmaitong group is higher than Xinmaitong group,while Xinmaitong group is higher than DAA-Ⅰgroup,and the comparison had significant deviation in statistics.(p<0.05).6.Na^+--K^+--ATPase Detection:The detection of the activity of Na^+--K^+--ATPase(U/mgprot) and in myocardial homogenate on rat models by Colorimetry indicated that:Compared with normal control group (331.37±80.26),the activity of Glutathione peroxidase in Heart failure model group(266.86±323.42) had decreased,and the comparison had significant deviation in statistics. (p<0.05).Compared with heart failure model group,DAA-Ⅰgroup(295.70±72.88),DAA-Ⅰ& Xinmaitong group(361.42±168.42) and Xinmaitong group had increased to different extents, and the comparison had significant deviation in statistics.(p<0.05);DAA-Ⅰ&Indomethacin group(163.57±64.45) and Indomethacin group(155.37±85.18) had decreased,and the comparison had significant deviation in statistics.(p<0.05).Among them,Xinmaitong group is higher than DAA-Ⅰ& Xinmaitong group,while DAA-Ⅰ& Xinmaitong group is higher than DAA-Ⅰgroup,and the comparison had significant deviation in statistics.(p<0.05).Conclusions:1.Both DAA-Ⅰand Xinmaitong could improve the Left ventricular function significantly ,and increase the content of Vrntricular myosin light chains(VMLC) significantly on Rat models. Effects of the combination therapy was better than either DAA-Ⅰor Xinmaitong alone, furthermore the effect of DAA-Ⅰwas stronger than that of Xinmaitong.2.Both DAA-Ⅰand Xinmaitong could resist myocardial cell injury,and increase the activity of Glutathione peroxidase and Na^+--K^+--ATPase significantly on Rat models.Effects of the combination therapy was better than either DAA-Ⅰor Xinmaitong alone,furthermore the effect of Xinmaitong was stronger than that of DAA-Ⅰ.3.Both DAA-Ⅰand Xinmaitong could decrease the content of Plasma ANP,ALD significantly on Rat models.Effects of the combination therapy of DAA-Ⅰand Xinmaitong had no significant advantage,furthermore the effect of DAA-Ⅰwas stronger than that of Xinmaitong.