The Effect Of Testosterone Receptor Protein In The Kidney Of 2K1C Rats And Its Mechanism

BackgroundIn recent years,with the increasing incidence of hypertension,the target organ damage has been paid more and more attention.Kidney damage mainly for renal vascular sclerosis,the early characteristic pathological changes of vascular smooth muscle showed compensatory hypertrophy and hyalinization,advanced intimal wall showed fibrinoid necrosis,stenosis or occlusion.High blood pressure can cause kidney damage,kidney damage can aggravate the occurrence and development of hypertension.Therefore,it is of great significance to clarify the mechanism of renal damage in hypertension.Testosterone is one of the important male hormones,which has been proved to be closely related to cardiovascular diseases.The biological activity of testosterone is achieved through the testosterone receptor(AR).Since 1978,AR was founded in rat ventricular myocytes,the research on AR has been gradually increased.AR has been proved to exist in vascular endothelial cells,smooth muscle cells,cardiac muscle cells,and in the kidney,blood and nervous system.Studies have indicated that changes in AR levels are associated with a variety of diseases,such as hypertension,coronary artery disease,prostatic hyperplasia,inflammatory factors,vascular remodeling,thrombosis,and so on.But the role of AR in hypertensive renal damage and its signal transduction mechanism is not clear.The excessive activation of the renin angiotensin system and the imbalance of mitogen activated protein kinase signaling(MAKPs)pathway play an important role in the occurrence and development of hypertensive renal damage.Mitogen activated protein phosphatase 1(MKP-1)is a specific regulator of MAPKs.A number of domestic and foreign research teams found that the coupling of AR and MAPKs pathways involved in many diseases.Our previous studies have confirmed that AR may be involved in hypertensive myocardial remodeling by coupling with the MAPKs signal transduction pathway.Is there any involvement of AR in hypertensive renal damage? Whether or not it is related to the MAPKs signal transduction pathway,no related reports.ObjectiveObjective to investigate the role of AR in hypertensive renal damage and its mechanism.MethodsAccording to the principle of randomized control,30 male Wistar rats were divided into normal control group,sham operation group and hypertension group,10 rats in each group.The renovascular hypertensive rat model of left renal artery stenosis was established by "two kidney one clip" method.The sham operation group only opened the abdominal cavity without ligation.Systolic blood pressure was measured by tail-cuff method.Kidney morphological structure was observed by Hematoxylin and eosin.Androgen receptor and mitogen activated protein kinase phosphatase-1 protein expression were detected by immunohistochemical.Result1 No significant change of SBP in normal control group(P < 0.05).There was no significant change in renal tissue structure(P> 0.05).Obvious reconstruction detected in the conrol rats' kidney2 No significant change of SBP in sham operation group(P > 0.05),and no significant changes were observed in renal morphology.Compared with the normal control group,the expression of AR and MKP-1 protein in the right kidney of sham operated group rats had no significant change(P > 0.05);3 Significant difference of systolic blood pressure were observed in renovascular hypertension group(F between group = 1211.779,F time =1613.225,F interaction =1537.050,P <0.001),and right renal remodeling,androgen receptor and mitogen activated protein kinase phosphatase-1 significantly decreased(P<0.01);4 A linear positive correlation is found between androgen receptor and mitogen activated protein kinase phosphatase-1 in hypertensive group(r=0.744,P=0.014),but not normal control group or the sham operation control group(r=0.457,0.436,P>0.05).ConclusionBoth AR and MKP-1 protein expression were down-regulation in hypertensive vascular remodeling,and linear correlation analysis shows that AR and MKP-1 protein expression are positive correlation.Suggesting that the change of androgen receptor protein expression level is involved in kidney remodeling,and androgen receptor is coupled with mitogen activated protein kinase signal transduction pathway.