右美托咪定预处理对脓毒症急性肾损伤大鼠肾功能、凋亡相关蛋白及Keap1-Nrf2/ARE信号通路的影响

Effects of Dexmedetomidine Pretreatment on Renal Function,Apoptosis-related Proteins and Keap1-Nrf2/ARE Signaling Pathway in Septic Acute Kidney Injury Rats

目的:探讨右美托咪定预处理对脓毒症急性肾损伤(SI-AKI)大鼠肾功能、凋亡相关蛋白及Keap1-Nrf2/ARE信号通路的影响。方法:随机将SD大鼠30只分为三组,各10只。在造模前10min,右美托咪定预处理组经耳缘静脉注射右美托咪定100μg/kg,假手术组和模型组则注射等量生理盐水,之后行CLP造模。造模24h后,观察肾脏组织病理学改变,肾功能指标,肾脏组织凋亡相关蛋白Bcl-2和Bax,细胞凋亡率以及肾脏组织中Keap1-Nrf2/ARE信号通路相关蛋白表达含量。结果:模型组肾脏组织结构完整度、清晰度下降,肾脏组织水肿严重,而右美托咪定预处理组上述病变明显减轻。右美托咪定预处理组血清BUN、SCr和UA水平高于假手术组,且低于模型组(均P<0.05)。右美托咪定预处理组肾脏组织Bax表达含量和细胞凋亡率高于假手术组,且低于模型组,而Bcl-2、总Nrf2、核Nrf2、HO-1和NQO1蛋白表达含量低于假手术组,且高于模型组(均P<0.05)。结论:右美托咪定预处理可通过激活Keap1-Nrf2/ARE信号通路,增加HO-1和NQO1蛋白表达而抑制肾组织细胞凋亡,有利于减轻SI-AKI,保护肾功能。

Objective:To investigate the effects of dexmedetomidine pretreatment on renal function,apoptosis-related proteins and Keap1-Nrf2/ARE signaling pathway in septic acute kidney injury(SI-AKI)rats.Methods:30 SD rats were randomly divided into three groups with 10 rats in each group.10 minutes before modeling,dexmedetomidine pretreatment group was injected with dexmedetomidine 100μg/kg through auricular vein,sham operation group and model group were injected with the same amount of normal saline,followed by CLP modeling.24 hours after modeling,renal histopathological changes,renal function indexes,apoptosis related proteins Bcl-2 and Bax,apoptosis rate and Keap1-Nrf2/ARE signaling pathway related protein expression levels in renal tissues were observed.Results:The structural integrity and clarity of the renal tissue in the model group were decreased,and the renal tissue edema was serious,while the above lesions were significantly reduced in the dexmedetomidine pretreatment group.Serum BUN,SCr and UA levels in dexmedetomidine pretreatment group were higher than those in sham operation group and lower than those in model group(all P<0.05).The expression level of Bax and apoptosis rate in kidney tissue of dexmedetomidine pretreatment group were higher than that of sham operation group and lower than that of model group,while the protein expression levels of Bcl-2,total Nrf2,nuclear Nrf2,HO-1 and NQO1 were lower than that of sham operation group and higher than that of model group(all P<0.05).Conclusion:Dexmedetomidine pretreatment can inhibit apoptosis of renal tissue cells by activating Keap1-Nrf2/ARE signaling pathway and increasing HO-1 and NQO1 protein expression,which is beneficial to alleviate SI-AKI and protect renal function.