Effects Of Dexmedetomidine Preconditioning Combined With Resveratrol On Myocardial Injury After Acute Kidney Injury In Diabetes Rats

Objective:To investigate the myocardial protective effect of resveratrol combined with dexmedetomidine preconditioning on acute renal injury in diabetic rats.Methods:Forty healthy male Wistar rats were fed a high-fat diet and injected intraperitoneally with1%streptozotocin 30mg/kg to establish a diabetes model.They were divided into 4 groups（n=8）by random number table:control group（Con group）,acute renal injury group（AKI group）,dexmedetomidine pretreatment group（DPre C group）,resveratrol combined with dexmedetomidine pretreatment group（Res+DPre C group）.The right kidney was resected,the left renal artery was blocked for 45 minutes,and the blood supply was restored to 4hours after the operation to prepare the AKI model;the DPre C group was infused with dexmedetomidine at a rate of 2μg·kg^-1·h^-130 min before AKI;Res+DPre C group:20mg/kg resveratrol was injected 15 min before AKI and 1 min before restoring left renal blood supply;Con group and AKI group were infused with the same amount of normal saline through the tail vein.The pathological changes of myocardial tissue were observed by HE staining,the apoptosis of myocardial tissue was observed by TUNEL staining,the expression of SIRT1,NF-κB p65,PGC-1α,Bcl-2,Bax,and the phosphorylation level of p-NF-κB p65 in myocardial tissue were measured by Western blot,and the serum levels of c Tn I,TNF-α,IL-17a,IL-10 were measured by ELISA.Results:Compared with the Con group,PGC-1αin the AKI group decreased and the rate of myocardial apoptosis decreased.In the AKI group and DPre C group,the level of p-NF-κB p65 increased,Bax increased,SIRT1 and Bcl-2 decreased,c Tn I,TNF-α,IL-17a increased,and IL-10decreased（P all<0.05）.In the Res+DPre C group,Bax decreased,and IL-10 decreased（P all<0.05）;Compared with the AKI group,the level of p-NF-κB p65 in the DPre C group and Res+DPre C group decreased,Bax decreased,the rate of myocardial apoptosis decreased,SIRT1,PGC-1α,Bcl-2 increased,c Tn I,TNF-α,IL-17a decreased,and IL-10increased（P all<0.05）;Compared with DPre C group,the level of p-NF-B p65 in Res+DPre C group decreased,Bcl-2 decreased,c Tn I,TNF-α,IL-17a decreased and IL-10increased（P all<0.05）.There was no significant difference in the expression of NF-κB p65 between the groups（P>0.05）.Conclusion:preconditioning with resveratrol and dexmedetomidine can inhibit the inflammatory response through the SIRT1-NF-κB-PGC-1αaxis,and effectively resist myocardial vulnerability after acute renal injury in diabetic rats.