| Background:Cardiorenal syndrome(CRS)is a clinical syndrome characterized by impaired function of one of the heart and kidneys,which in turn,contributes to the progressive impairment of the function of another and ultimately to the failure of two organs.In 2008,Ronco classified heart-and-kidney syndromes as type 5,and definite type 2 CRS by chronic heart failure leading to chronic kidney disease,hemodynamic disturbances,neurohormonal mechanisms active,and accumulation of uremic toxins,inducing Myocardial fibrosis and left ventricular remodeling,and further aggravate renal dysfunction,poor prognosis in patients with high mortality,without any effective treatment and prevention.Therefore,to improve hemodynamics and inhibit fibrosis is the key point of prevention and treatment of type 2 CRS.In recent years,studies have shown that indoxyl sulfate(IS)may be associated with heart-kidney fibrosis in rats with type 2 heart-kidney syndrome.As one of the protein-bound uremic toxins,IS can not be removed by dialysis,accumulating in the body easily induce myocardial fibrosis,but also activate immune cells to induce coronary plaque formation and increase the risk of cardiovascular events.Therefore,the level of in vivo serum IS can indirectly reflect the degree of cardiac fibrosis in type 2 CRS.Higenamie is an active ingredient isolated from the aconite,as part of the beta receptor agonist;its positive inotropic effect can improve heart failure to some extent.In addition,to the arsenica can expand peripheral blood vessels;rise up coronary blood flow and myocardial perfusion,reduced ischemia-reperfusion injury,with potential anti-myocardial fibrosis.However,at present,there are no relevant research and literature reports about the higenamie on the inhibition of myocardial fibrosis and the improvement of heart and kidney function of type 2 CRS rats at home and abroad.Therefore,in this study,rat models of type 2 heart-kidney syndrome were established by coronary artery left anterior descending coronary artery ligation(CAL)combined with right kidney extirpation and left renal artery ligation with 5/6 subtotal nephrectomy(STNx)Intraperitoneal injection of different doses of higenamie compared with CRS model rats,analysis of heart and kidney function,tissue fibrosis area,changes in expression of fibrosis factor and serum IS levels.To research whether higenamine can inhibit myocardial fibrosis,reduce left ventricular remodeling,thereby improving renal function,blocking type 2 CRS rat heart and kidney interaction,heart and kidney play a synchronous role in the protection of type 2 CRS drugs Treatment to find potential targets.Part ? The development of model rats with type2 cardiorenal syndromeObjective:A 5/6 subtotal nephrectomy(STNx)procedure was performed through the combination of left anterior descending coronary artery(CAL)with right renal extirpation,anterior superior branch of the left renal artery,anterior descending artery,and posterior branch ligation 2 CRS rat model induced myocardial fibrosis,the effect of heart and kidney damage were evaluated for the follow-up to arsenic disulfide drug intervention experiments and heart and kidney fibrosis lay the experimental foundation.Methods:CRS type2;Coronary Artery Ligation;Subtotal Nephrectomy;Rat modelSD rats(n=28)were randomly divided into model group(n=20)and sham operation group(n = 8).Under the guidance of ECG,CAL-induced left heart failure.One week later,type 2 CRS rat model was took 5/6 STNx operation via removal of the right kidney,ligation of anterior superior branch,anterior descending artery and the dorsal ramus of the left renal artery.The cardiac function,fibrosis index were compared with the sham operation group to evaluate the effect of myocardial fibrosis and heart and kidney function damage in model rats.Results:1.13 were successful in modeling,7 survived and the survival rate was 53.84%.2.Ultrasound,blood biochemistry and other indicators showed CRS rat heart and kidney function was significantly impaired;3.Heart and kidney sections HE,MASSON staining show a markedly increase of collagen deposition in CRS model rat heart and kidney,the collagen area increased significantly,the organization showed fibrosis changes.Conclusion:The method used to construct type 2 CRS rat model in this experiment is simple,short cycle,and maintains the organ integrity on the basis of obviously inducing chronic heart and kidney function damage and myocardial tissue fibrosis.In line with type 2 CRS pathophysiological status,is an ideal model for the study of 2 heart-kidney syndrome animal model can be used for subsequent drug intervention and anti-fibrosis experimental study.PRAT ? The protective effects of higenamine on Heart and Kidney of Type2 CRS Model RatsObjective:To investigate whether the higenamine take a protective effective on heart and kidney synchronously by inhibiting myocardial fibrosis and ameliorating left ventricular remodeling that result in improvement of cardiorenal function.Methods:The above method was used to construct a rat model of type 2 CRS.The model rats were randomly divided into model group,low,medium and high dose of norfloxacin and western medicine group.Intraperitoneal injection of 0.5mg/kg,1.5mg/kg,4.5mg/kg of higenamine,Western medicine group given perindopril 2mg/kg gavage,the model rats was given the same amount of saline.Results:The survival rate of the rats treated with higenamine improve significantly with the increase of the dose,compared with the model group,.The echocardiographic and biochemical tests showed that the heart and kidney function gradually improved and the serum IS level decreased gradually.Masson staining of heart and kidney tissue sections showed that the area of collagen decreased gradually,and the expression intensity of collagen fibers Collagen ? and TGF-? decreased gradually with immunofluorescence staining.Conclusions:Adenylate inhibited myocardial fibrosis in type 2 CRS rats in a dose-dependent manner and decreased the area of myocardial collagen and the expression of fibrosis factors Collagen ? and TGF-?.Ameliorating the potential of promoting the role of IS excretion may be related to the improvement of hemodynamic and renal function.The inhibition of myocardial fibrosis by ameba could be related to the promotion of IS excretion and the decrease of serum IS levels.The effect of demeton method on myocardial fibrosis may be related to interfering with the expression of fibrosis signaling pathway TGF-?/Smad or fibrosis bypass Erkl/2.To arsenica in inhibiting myocardial fibrosis at the same time,heart and kidney function gradually improved survival rate increased,showing a dose-dependent role of heart and kidney protection. |
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