Effect and mechanism of remimazolam on acute renal ischemia-reperfusion injury in rats
Objective To investigate the effects of remimazolam on renal ischaemia-reperfusion injury(IRI)in rats based on Toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling pathway.Methods Thirty-six SPF-grade healthy male SD rats,8 weeks old,weighing 220-250 g,were divided into three groups using the random number table:sham group,renal ischemia-reperfusion group(IRI group),and renal ischemia-reperfusion+remimazolam group(IRI+R group),with 12 rats in each group.The rat renal ischemia-reperfusion model was established by clamping the bilateral renal arteries for 50 min and then reperfusion in IRI group and IRI+R group.The rats were infused with 10 mg/kg remimazolam for 15 min via the tail vein before ischemia in IRI+R group,and an equal volume of saline in IRI group and sham group at the same time.After reperfusion for 24 h,the rats were sacrificed,then the heart blood was collected to detect the levels of urea nitrogen(BUN)and creatinine(Cr),the renal tissues of rats were taken to observe the renal histopathology by HE staining,the apoptosis was observed by TUNEL method,and NF-κB and TLR4 expressions were detected by immunohistochemistry.Results Compared with sham group,blood BUN and Cr levels were increased in IRI group(P＜0.05),the renal histopathological score was significantly increased(P＜0.05),the renal tubular cell apoptosis was significantly increased(P＜0.05),and the expressions of NF-κB and TLR4 were elevated(P＜0.05).Compared with IRI group,blood BUN and Cr levels were decreased in IRI+R group(P＜0.05),the renal histopathological score was reduced(P＜0.05),the renal tubular cell apoptosis was reduced(P＜0.05),and the expressions of TLR4 and NF-κB were decreased(P＜0.05).Conclusion Remimazolam pretreatment can reduce the renal ischaemia-reperfusion injury in rats by inhibiting TLR4/NF-κB signaling pathway and attenuating the inflammatory response.
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