| PrefaceUremic cardiomyopathy is a common complication of uremia.Unless a kidney transplant is performed,neither hemodialysis nor peritoneal dialysis can be fully improved to threaten the patient's quality of life.The pathogenesis of uremic cardiomyopathy is very complicated,and multiple neuro-humoral factors are involved.The main molecular biological mechanisms include renin-angiotensin system(RAS),Excessive excitation of endothelin system,thrombon-prostaglandin system,of which the role of RAS is very accurate.And uremia cardiomyopathy involves a variety of inflammatory mediators,These include platelet—derived growth factor(PDGF).RAS is an important pathway in the cardiomyopathy of uremia,multiple studies have shown that,renin-angiotensin inhibitor(RASI)can delay myocardial fibrosis,mortality can be effectively reduced in patients including MHD.The down-regulated signal transduction of PDGF can alleviate myocardial fibrosis.Recent studies have shown that AT1 R activation can directly increase the transcription level of PDGF and play the role of fibrosis in addition to growth factor ?,because of the distribution of PDGF and its wide range,this role of angiotensin II will involve more organs and tissues,and the effect will be magnified further.Therefore,this research first established uremic cardiomyopathy animal model of rats,to detect the expression level of myocardial tissue is PDGF,at the same time observe the application of angiotensin receptor antagonist(ARB)?1 type treatment can reduce the uremic cardiomyopathy rats is PDGF expression level,reduce the degree of myocardial injury model in rats.Second,we choose regular hemodialysis patients,give angiotensin receptor antagonist(ARB)?1 type treatment,the absence of large fluctuations in blood pressure,observe the patient's heart function and the change of the serum level of PDGF,whether larger doses of the ARB can improve cardiac function in this part of the hemodialysis patients;The serum PDGF level also fluctuates.Part one The effect of angiotensin ?1 receptor antagonists on platelet—derived growth factor in the uremic cardiomyopathy rats.Objective:This study through the establishment of uremic cardiomyopathy animal model of rats,to detect the expression level of myocardial tissue PDGF,at the same time observe the application of angiotensin receptor antagonist(ARB)?1 type treatment can reduce the uremic cardiomyopathy rats PDGF? receptor(PDGFR ?)expression level,reduce the degree of myocardial injury model in rats.Methods:First,the renal artery branch ligation method was used to establish 5/6renal resection of the rat model,and then the isopropylenergic injection was administered to complete the heart failure model of the rat.Rats were divided into three groups: valsartan group(ARB group): valsartan irrigation and stomach n= 32;Simple renal large-cut non-intervention group(NX group): the volume of the volume injected with water was injected into the stomach,and n= 32;Sham operation group(sham):wait for volume injection with water for the stomach,n= 20.All rats were regularly tested for the ratio of blood pressure,albumin/urinary creatinine.The rats in the 5/6kidneys began to enter the formal trial 7 days after the second operation.At 0 weeks and6 weeks,10 weeks and 11 weeks,8 rats were executed in each group.The blood and myocardium and kidney tissue were respectively taken for biochemical detection and histopathological examination.Under optical microscope,the degree of myocardial fibrosis was observed,Rona standard score was performed,and the Image Pro Plus software 6.0 Image analysis system was applied to calculate the collagen volume fraction(CVF)in myocardial tissue.The expression level of PDGF receptor(PDGFR)in myocardial tissue was observed by immunohistochemistry.The content of PDGFR in myocardial tissue was detected by Western Blot.Results:There was a significant increase in the 7th week of the rat tail artery systolic blood pressure in all 5/6 kidneys.The increase of arterial blood pressure in ARB group was significantly lower than that in NX group.The increase of SCr and BUN level in the ARB group was significantly lower than that of NX group.The myocardial pathological examination of valsartan group and NX group showed that the cardiomyocytes of the two groups of rats showed hypertrophy,permutation disorder andsignificantly increased intercellular mass.However,the lesion degree of valsartan group was less than that of NX group and the Rona score of treatment group was lower than that in the control group.The difference was significant,P< 0.05.The results of immunohistochemistry index showed that the expression levels of PDGFR in ARB group and NX group were significantly higher than that in sham group,and the expression level of PDGFR in ARB group was significantly lower than that of NX group,and the difference was significant,P< 0.05.Western Blot results showed that the expression levels of PDGFR in ARB group and NX group were significantly higher than that in sham group,and the difference was significant,P< 0.05.The expression levels of PDGFR in ARB group were significantly lower than NX group,and the difference was significant,P< 0.05.Conclusion:There was obvious histological damage in the myocardial myocardial myocardial model of the rat.The expression levels of PDGFR were significantly elevated in the myocardial localized inflammatory mediators,suggesting that PDGF and its receptors were involved in the myocardial damage of the rats with uremia cardiomyopathy;ARB valsartan treatment of myocardial damage in rats significantly lighter than not medicine control group,valsartan treatment of rat myocardial PDGFR expression level is obviously lower than the control group,suggested PDGF and its receptor mediated uremia myocardial damage,partly through Ang ? and its type 1receptor pathway.Key words: 5/6 nephrectomy,platelet—derived growth factor receptor,angiotensinPart two The effect of angiotensin ?1 receptor antagonists on the levels of platelet—derived growth factor in patients with maintenance hemodialysis.Objective:Select the primary disease of only kidney disease of hemodialysis patients,give patients with angiotensin receptor antagonist ?1 type(ARB)treatment,the absence of large fluctuations in blood pressure,observe the patient's heart function and the change of the serum level of PDGF,whether larger doses of the ARB can improve cardiac function in this part of the hemodialysis patients;Whether the inflammatory mediators PDGF also fluctuates.Methods :The 41 patients with primary renal disease and regular hemodialysis were randomly divided into two groups: valsartan treatment group(treatment group),n=22;Control group n=19;Patients in the treatment group included valsartan(no other type of RASI)in the type of blood pressure medicine;In the control group,any of the RASI was not included in the blood pressure drug,and the other types of antihypertensive drugs and dosage should be appropriately increased to match the blood pressure matched by the control group and the treatment group,and the observation time was 3 months.The serum PDGF levels were detected in the treatment group and the control group before and after the experiment.Results:After 3 months of large dose of valsartan oral,LVEDD,EF,and the treatment group compared with control group,the A/E and other indicators are improved to varying degrees,the EF values of treatment group was obviously higher than that of control group,P < 0.05).The serum PDGF level was significantly decreased after treatment with valsartan treatment group,and the difference was significant before treatment,P< 0.05.The serum PDGF level did not change significantly after the three-month observation period of the control group,and the difference was not significant.P> 0.05.Conclusion:Uremic cardiomyopathy patients increased significantly,serum levels of PDGF after valsartan treatment,improve synchronization with heart EF value of serum levels of PDGF decreased,serum level of PDGF may be monitoring the hemodialysis patients with uremia simple level. |
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