Effects Of RDN On RAAS And TH Protein Expression In Diabetic Rats

Objective: This study was aimed to investigate how Renal Denervation(RDN)affects heart weight index,cardiomyocyte morphology,Renin Angiotensin Aldosterone System(RAAS)and expression of Tyrosine Hydroxylase(TH)in left ventricular tissue of diabetic rats.Methods: Thirty-two male Sprague-Dawley rats were randomly divided into 4 groups:sham operation group(SHAM group,n = 8),diabetes group(DCM group,n = 8),benazepril group(DCM + DRUG group,n = 8),renal denervation group(DCM + RDN group).After a week of adjustable feeding,rats in the DCM group,DCM + DRUG group,and DCM + RDN group were injected with Streptozotocin(STZ,55mg/kg)in the left lower abdomen at once.After seventy-two hours,blood glucose in tail vein of rats was measured,Taking blood glucose ?16.7mmol/L as the main criteria for judging the success of the diabetes model,it showed that all 24 rats were successfully modeled.The same volume of citric acid buffer was injected intraperitoneally in the SHAM group.After four weeks of rearing,rats in the RDN group was subjected to renal sympathectomy by physical cutting under the microscope and phenol chemical ablation,and electrical stimulation was performed to verify the denervation effect.As for the SHAM group,merely renal arteriovenous was isolated.Rats in the DCM + DRUG group were given drug intervention(benazepril gavage,10 mg / kg / d),and rats in the other three groups were given the same volume of saline.Rats in each group were reared for 8 weeks with the same food,water,light,rest and other conditions.The final grouping statistics included:SHAM group(n = 8),DCM group(n = 7),DCM + DRUG group(n = 8),DCM + RDN group(n = 6).After observing and recording the general indexes of the rats in each group(blood glucose,body weight and heart weight),the rats in each group were anesthetized with 10% chloral hydrate(3ml/kg)and exsanguinated to death,with plasma and heart tissue samples collected.Enzyme-linked immunosorbent assay(ELISA)was used to detect plasma noradrenaline,Renin,Angiotensin II(AngII),Aldosterone(ALD),Brain natriuretic peptide(BNP)levels;Hematoxylin-Eosin(HE)staining was adopted to observe the morphology of cardiac myocardial cells,myocardial interstitial hyperplasia and edema;Western-blot method(Western-Blot,WB)was used to detect the relative expression of TH protein in myocardial tissue in rats of each group.Results:1.After 12 weeks of breeding,compared with the SHAM group,the DCM group,the DCM + DRUG group and the DCM + RDN group all showed typical symptoms,including depression,dark fur,diarrhea,cataract and even death of some rats.2.Compared with the SHAM group,DCM group,DCM + DRUG group and DCM +RDN group all showed weight loss,blood glucose increase,and heart weight index increase(P <0.05);compared with the DCM group,DCM + DRUG group,DCM + RDM group showed heart weight decrease(P <0.05).3.The results of HE staining showed that myocardial cells were well arranged in the SHAM group without mesenchymal hyperplasia or edema,while myocardial cells in the DCM group were in varied shapes and sizes and arranged in disorder,with severe mesenchymal edema,hyperplasia,and infiltration of inflammatory cells.The morphology and arrangement of myocardial cells in the DCM + DRUG and DCM + RDN groups were poor,and the interstitial fibrosis and inflammatory cell infiltration were improvedcompared with the DCM group.4.Compared with the SHAM group,the levels of plasma NE,BNP,Renin,and ALD in the DCM group,DCM+DRUG group,and DCM+RDN group(P <0.05).Compared with the DCM group,the levels of plasma NE,BNP,and Renin in the DCM + RDN group were reduced(P<0.05),the plasma ALD level in the DCM + DRUG group was reduced(P <0.05),and the plasma AngII level(P <0.05)in the SHAM group,DCM + DRUG group,and DCM + RDN group were reduced.Compared with the DCM + DRUG group,the plasma NE level decreased and the BNP level increased in the DCM + RDN group(P<0.05).5.Compared with the SHAM group,the relative expression of left ventricular TH in DCM group,DCM + DRUG group and DCM + RDN group(P <0.05)was significantly increased.Compared with the DCM group,the relative expression of left ventricle TH in the DCM + RDN group(P> 0.05)had a downward trend.Conclusion: 1.hyperplasia,edema and inflammatory cell infiltration occurred in ventricular muscular tissues of diabetic rats to different degrees.2.RDN can reduce severity of heart failure in diabetic rats.3.RDN may inhibit systemic sympathetic nerve activity by reducing renin and aldosterone secretions,thus delaying the progress of diabetic cardiomyopathy.4.The expression of TH protein in the left ventricle of diabetic rats was significantly increased,suggesting that sympathetic nerve activity in left ventricle was increased,but RDN has its limitations for inhibiting the cardiac sympathetic nerve activity.