Effect Of Dexmedetomidine On Oxidative Stress With Rhabdomyolysis-induced Acute Kidney Injury In Rats

Sports training and military training usually need a lot of exercise,and severe muscle damage is caused by unreasonable long-term strenuous exercise.Overtraining leads to rhabdomyolysis,and acute kidney injury(AKI)occurs when substances from muscle cells enter the blood after myolysis.Therefore,it is necessary to prevent the occurrence of the dissolution of rhabdoid muscle and avoid kidney damage.Oxidative stress plays a variety of roles in kidney disease.It can not only activate a variety of signaling pathways,but also regulate metabolism.When excessive reactive oxygen species are active,it can cause damage to the body.Dexmedetomidine(DEX)has shown that it can inhibit oxidative stress,anti-apoptosis,as well as can also improve acute kidney injury induced by sepsis and ischemia-reperfusion.However,the function and mechanism of DEX intervention in acute kidney injury induced by rhabdomyolysis have not been reported yet,and further research is needed.Objective:Rhabdomyolysis-induced acute kidney injury model was established to observe the changes of renal function,histopathology and oxidative indexes,and whether Dexmedetomidine as an intervention drug plays a protective effect on the kidney.Methods:42 SD rats were randomly assigned to blank control group(CN,n=6),acute kidney injury group(AKI,n=18)and dexmedetomidine intervention group(DEX,n=18).In addition to the immediate observation in the control group,the other two groups were divided into three time points: 1h,6h and24 h after the injection of glycerin.Each group had 6 rats.The rats were injected intramuscularly with glycerol to develop a model of acute kidney injury caused by rhabdomyolysis.The intervention group was intraperitoneally injected with 30μg/kg DEX 30 minutes before injection of glycerolsame.The control group was intraperitoneally injected with the same amount of normal saline in the same way and time.At the corresponding time points,the renal function,the contends of serum MDA and SOD,the degree of renal tissue pathological damage,and the nucleoprotein expression of Nrf2 by Western blot and the total protein expression of HO-1 by Western blot and immunohistochemical methods were detected in rats.Results:1.Changes of renal functionCompared with CN group,serum creatinine,blood urea nitrogen and creatine kinase in model group were all increased at each time(P<0.05 or P<0.01),serum creatinine and blood urea nitrogen were the highest at 24 h after glycerol injection,and creatine kinase were the highest at 6h after glycerol injection.However,compared with the AKI group at the same time,both blood urea nitrogen and creatine kinase in the DEX group decreased at 6h(P<0.01),and both blood urea nitrogen and creatinine were significantly decreased at 24h(P<0.01),which could not be reduced to the level of the control group.2.Changes of serum MDA and SOD contentsCompared with the control group,MDA content in AKI group increased with time gradient,and the SOD vitality declined progressively(P<0.01).In the comparison of DEX group and the corresponding period point AKI group,the SOD activity in serum increased at each time(P<0.01),and the content of MDA in serum decreased at 6h and 24h(P<0.01),but the intervention administration could not return to the normal level.3.Pathological changes of renal tissueLight microscopy showed that renal tubules were damaged to various degrees in the AKI group,and tubular protein and cell necrosis could be observed,and renal tissue damage was alleviated in the rats treated with DEX intervention drugs.In the renal tubular injury score,except the control group,the scores of the remaining groups were progressively improved.The DEX group score at 6h and 24 h was apparently lower than the same period AKI group(P<0.01).4.Expression changes of Nrf2 nucleoprotein in kidney tissueWestern blot showed that the nucleoprotein expression of Nrf2 in AKI group were increased at 1h and 24 h compared with the control group(P<0.01).Compared with the model group,the Nrf2 nucleoprotein was decreased at 1h in the DEX intervention group(P<0.01),and the Nrf2 nucleoprotein was significantly increased at 6h and 24 h in the DEX intervention group(P<0.01).5.Expression changes of HO-1 total protein in kidney tissueImmunohistochemical results showed that the expressions of HO-1total protein positive granules were mainly distributed in renal tubules.The HO-1 total protein in AKI group was elevated at all time points compared with the control group(P<0.05 or P<0.01).Compared with the AKI group,the HO-1 total protein was significantly elevated at 6h and 24 h in the DEX intervention group(P<0.01).Western blot showed that the total protein expression of HO-1 in AKI group were increased at 6h and 24 h compared with the control group(P<0.01).Compared with the model group,the HO-1total protein was significantly increased at 6h and 24 h in the DEX intervention group(P<0.01).Conclusion:1.Oxidative stress injury is involved in the pathophysiological process of acute kidney injury induced by rhabdomyolysis in rats.2.Pre-administration of DEX can alleviate acute kidney injury induced by rhabdomyolysis in rats,the mechanism of action may be related to the activation of Nrf2/HO-1 signaling pathway,thus alleviating oxidative stress injury in renal tissue.