Study On The Protective Effect Of Esmolol In Rats With Sepsis-induced Acute Kidney Injury

Objective To investigate the underlying mechanism of esmolol attenuating sepsis-induced acute kidney injury in rats through cell cycle arrest.Methods 48 male SPF rats were selected,and the rats were randomly divided into sham operation group(Sham group),sepsis group(CLP group),and esmolol group(ES group).In each group,16 rats were also randomly divided into 6-hour group and 24-hour group.The rats in the Sham group received only the abdomen closed after opening the abdomen.And the rats in the CLP and ES group received the CLP.For all the rats,the internal jugular vein catheterization was performed,and the normal saline(1ml/h)was infused through the internal jugular vein in Sham and CLP group.The ES group was infused with esmolol(15mg/kg/h,initially infused with1ml/h,adjust the infusion rate according to the heart rate).The rats in each group were continuously infused with normal saline or esmolol diluent for 6 hours.And then,the rats in each group were sacrificed at the corresponding time points with 6h and 24 h after the operation,and the serum and tissue samples were collected for further examination.After centrifugation,the rat blood was collected to detect the contents of BUN and Cr by ELISA.For every sample,the left kidney underwent p53 immunohistochemical detection.The right kidney tissue was stored in a-80℃ultra-low temperature environment,and the tissue was homogenized before the further detection.A part of the homogenate underwent Western Blot analysis,to detect the protein expression level of TLR-4,NF-κB,and ATM.Another part of the homogenate was tested by ELISA,to exam the TIMP-2 and IGFBP-7 level.Results(1)TLR-4 and NF-κB in ES6 h group and CLP6 h group were significantly higher than Sham6 h group(P<0.05).And these two factors in CLP24 h was also significantly higher than Sham24h(P<0.05).But in ES24 h group,TLR-4level was higher than CLP24 h.Compared with the CLP24 h group,the level of NF-κB in the ES24 h group was not significantly lower(P>0.05).We tested serum Cr and BUN levels in each time,and the result showed that the CLP group was significantly higher than that of the Sham group(P<0.05).(2)The serum Cr and BUN of the ES6 h group were also significantly higher than that of the Sham group(P<0.05).But the ES24 h group showed a decreasing trend compared with CLP24 h group(P<0.05).(3)Except that the TIMP-2 level in the ES24 h group was not statistically significant lower compared with CLP24 h group(P>0.05),the levels of IGFBP-7,TIMP-2,ATM and p53 in CLP group and ES group were significantly higher than those in the Sham group at each time(P<0.05).And ES group was lower than CLP group(P<0.05)in each period.Conclusions Esmolol may affect the key proteins of TLR-4/NF-κB/ATM/p53 pathway.It can reduce inflammation and renal tubular epithelial cell cycle block,and promotes the recovery of renal function in SAKI rats,and then protects SAKI rats.