Effect Of Tilishengmai Decoction On Angâ…¡,Angâ…¡ Receptor And Its Signal Conducts In The Rats Model Of CHF

Objective: Tinglishengmai decoction (It conposed of Red Ginseng,Pepperweed Seed,Chinese Magnolivine Fruit,Dwarf Lilyturf Tuber, Herbaceous peony,Radix astragali,Leonurus siribicus,Salvia miltiorrhiza)have efficacy of yiqiwenyang,huoxuelishui.It is valid anagraph through our team clinical observation.It has fine therapeutic efficacy.To study the potential mechanism of Tilishengmai decoction treating CHF,according to reference documents,CHF model was established by constriction of abdominal aorta,at the same time,the animal was interfered with medicine,to observe the effect on Hemodynamics,the content of AngⅡin plasma;to observe the effect of the expression of myocardial tissue AT1 receptor and its signal conducts PKC.Moreover,we use Hedyeing to observe the effect on pathomorphology of myocardial tissue.Methods:PartⅠEffect of Tinglishengmai decoction on Hemodynamics and myocardial tissue pathomorphology of CHF ratsSelect Wister rats 60,rats drink water and take food.freely,and were raised in sanitary experiment lab that temperature was 18℃～22℃,bright and dim alternate every 12 hours. After 1 week,divided into 5 groups randomly,for each group 12 rats:the sham operated group,the model group,the high-dose Tinglishengmai decoction group,the low-dose Tinglishengmai decoction group,the xinbaowan control group. According to reference, CHF model was established by constriction of abdominal aorta,sham operated group was the same operation but constriction of abdominal aorta.Rats in each group were given stomach-perfusion one day and erery time the drug volume was calculated by 1ml/100g. After 4 weeks, control drug or treatment drug was given in each treatment group and distilled water was given to sham operated and model group. At the end of the experiment, the rats were forbidden to eat for 12h.The rats were anaesthetized,draw off right common carotid artery and drive off breast and ascending aorta,all rats were injected 0.3% Calparine into vena caudalis,after heparinization,intubate right common carotid artery in order to record blood pressure,intubate apex of heart in order to record left ventricle pressure,to place number 2 electromagnetic flowmeter detecting head,to measure aortic blood flow and to record HR,LVSP,LVEDP,±dp/dtmax,though MS4000 physiograph.We got tissue from apex of heart,soak in 4% Glutaric Dialdehyde,affix to provide for observation of the light microscope .PartⅡEffect of Tinglishengmai decoction on AngⅡ,AngⅡreceptor and its signal conducts PKC on CHF rats The group distribution an drug-given were the same as above.At the 12th week since the experiment formally started,the rats were killed 12 hours after fasting of last time.The rats were anaesthetized and their blood were drawn out,put them into test tube of heparin the and EDTA respectively,the blood sample was made centrifugation with low temperature,mearesured the content of AngⅡin plasma by radio immunoassay.What's more,take some myocardial tissue from apex of heart,soak in 4% Glutaric Dialdehyde,affix to provide for observation of the expressions of AT1 receptor and signal conducts PKC. All the data were made statistics analysis with SPSS 13.0 software.Result:PartⅠEffect of Tinglishengmai decoction on Hemodynamics and myocardial tissue histomorphology of CHF rats1 The common behavior of all ratsThe 5 in 60 rats died when modeling and later died when treating.Therefore,48 rats in fact.During the process of experiment,the rats'color pattern of sham operated group was luster,drink and food normally,and having sensitive reflection.The model group rats were thin,thirsty,fur in disorder and withered,body to heaped up,activity to decrease.At the end stage of experiment,the modle group rats were more thiner even lower than before and oedema.After the treatment,the rats of treating group became well. 2 Effect of Tinglishengmai decoction on Hemodynamics of CHF ratsCompare with sham operated group,the LVEDP and HR of model group were significantly increased(P<0.05). Howerver, the LVSP,±dp/dtmax,MAP were obviously lower(P<0.05 or P<0.01),the heart systole and diastolic function of model group rat'was obstacled. After the intervention of medicine,the LVEDP and HR of the treatment groups were significantly decreased(P<0.05),the LVSP,±dp/dtmax,MAP were obviously increased(P<0.05 or P<0.01). What's more, the±dp/dtmax of high-dose group was higher than±dp/dtmax than the control group(P<0.01);the±dp/dtmax of low-dose group was lower than the control group.3 Effect of Tinglishengmai decoction on tissue pathomorphology of CHF ratsResult to show, the cardiac muscle cell of sham operated group was texture clear, shape was normal, endochylema's color was well-distributed, mesenchymal cell have no hyperplasy and no synathroisis. The model group rats'cardiac muscle fiber was not normal, texture disappeared, mesenchymal cell was oedema in light degree. The cardiac muscle cellular nucleus was analosis, dyeing was darken. The treating groups'condition was more lighter than model group.PartⅡEffect of Tinglishengmai decoction on AngⅡ,AngⅡreceptor and its signal conducts PKC on CHF rats 1 Effect of Tilishengmai decoction on contens of AngⅡin plasma of ratsCompare with sham operated group,the content of AngⅡin plasma of model rats were significantly increased(P <0.01);After the intervention of medicine,the contents of AngⅡin plasma of each treatment group were reduced(P<0.01).And the content of AngⅡin plasma in high-dose group was obviously reduced than the control group and low-dose group(P<0.01).There was no marked difference between the low-dose group and control group(P>0.05).2 Effect of Tinglishengmai decoction on experssion of AT1 receptor of CHF ratsThe expression of AT1 receptor in myocardial tissue of model rats were significantly increased(P<0.01);After the intervention of medicine,the expression of AT1 receptor in myocardial tissue of each treatment group were reduced(P<0.01).And the expression of AT1 receptor in myocardial tissue in low-dose group was reduced than the control group and high-dose group,but there was no marked difference among the low-dose group,high-dose group and control group(P>0.05). 3 Effect of Tinglishengmai decoction on experssion of PKC of CHF ratsCompare with sham operated group,the expression of PKC in myocardial tissue of model rats were significantly increased(P<0.01);After the intervention of medicine,the expressions of PKC in myocardial tissue of each treatment group were reduced(P<0.01). And the expression of PKC in myocardial tissue in high-dose group was obviously reduced than the control group and low-dose group(P<0.01).There was no marked difference between the low-dose group and control group(P>0.05).Conclusions:1 Tinglishengmai decoction could amendment affection of cardiac muscle histologic obviously,after treatment,result to show that the apomorphosis of cardiac muscle cell was abatement or disappearance.The cardiac muscle to line up in order,the mesenchymal cell have no synathroisis obviously. It proved that Tinglishengmai decoction could protect cardiac muscle cell.2 Tinglishengmai decoction could significantly increase MAP, LVSP and±dp/dtmax meanwhile reduce LVEDP, improve the heart diastolic and contracting function, as well as increase compliance of heart muscle.3 Tilishengmai decoction could reduce the concent of AngⅡin plasma of CHF rats,reduce the expressions of AT1 receptor and PKC,restrain the hyperactivity of RAS system,and to achieve effect of resisting CHF.This is one of mechanism of action that Tinglishengmai decoction treat CHF.