瑞马唑仑对大鼠急性肾缺血再灌注损伤的影响及机制  

Effect and mechanism of remimazolam on acute renal ischemia-reperfusion injury in rats

作　　者：高建辉 薛莹[1] 张佳齐 王妮荣 余淑珍[2] GAO Jianhui;XUE Ying;ZHANG Jiaqi;WANG Nirong;YU Shuzhen(School of Anesthesiology,Shanxi Medical University,Taiyuan 030001,China;Department of Anesthesiology,Fifth Clinical Medical College of Shanxi Medical University,Shanxi Provincial People′s Hospital)

机构地区：[1]山西医科大学麻醉学院,太原030001 [2]山西医科大学第五临床医学院,山西省人民医院麻醉科,太原030012

出　　处：《山西医科大学学报》2024年第5期621-626,共6页Journal of Shanxi Medical University

摘　　要：目的基于Toll样受体4(TLR4)/核转录因子-κB(NF-κB)信号通路探讨瑞马唑仑对大鼠肾缺血再灌注损伤(IRI)的影响。方法SPF级健康雄性SD大鼠36只,8周龄,体质量220~250 g,采用随机数字表法将大鼠分为3组(n=12):假手术组(sham组)、肾缺血再灌注组(IRI组)、肾缺血再灌注+瑞马唑仑处理组(IRI+R组)。IRI组和IRI+R组采用夹闭双侧肾动脉50 min后恢复灌注的方法制备大鼠肾缺血再灌注模型。IRI+R组于缺血前15 min经尾静脉输注瑞马唑仑10 mg/kg,IRI组和sham组同时输注等容生理盐水。恢复灌注24 h后处死大鼠采集心脏血,检测尿素氮(BUN)、肌酐(Cr)水平;取肾脏组织,HE染色观察肾组织病理变化;TUNEL法检测细胞凋亡;免疫组化检测NF-κB和TLR4表达。结果与sham组相比,IRI组经缺血再灌注24 h后,血BUN、Cr水平升高(P<0.05),肾组织病理评分明显增大(P<0.05),肾小管细胞凋亡明显增多(P<0.05),NF-κB和TLR4表达升高(P<0.05);与IRI组相比,IRI+R组经缺血再灌注24 h后,血BUN、Cr水平降低(P<0.05),肾组织病理评分减少(P<0.05),肾小管细胞凋亡减少(P<0.05),TLR4及NF-κB的表达均下降(P<0.05)。结论瑞马唑仑预处理可减轻大鼠肾缺血再灌注损伤,其机制可能与抑制TLR4/NF-κB信号通路、减轻炎症反应有关。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.

关 键 词：瑞马唑仑 肾缺血再灌注损伤 预处理 TLR4/NF-κB 炎症 

分 类 号：R614[医药卫生—麻醉学]