摘要
目的评价异丙酚预先给药对肝缺血再灌注小鼠肾损伤时动力相关蛋白1(Drp1)Ser637去磷酸化的影响。方法SPF级健康雄性C57小鼠30只,体重20~25 g,采用随机数字表法分为3组(n=10):假手术组(S组)、肝缺血再灌注组(HI/R组)和异丙酚预先给药组(P组)。建立小鼠肝缺血再灌注模型。P组于术前30 min腹腔注射1%异丙酚30 mg/kg,S组和HI/R组腹腔注射等容量生理盐水。于再灌注6 h时经左心室采血检测血清尿素氮(BUN)及肌酐(Cr)水平,TUNEL染色法确定肾组织细胞凋指数亡,采用Western blot法检测肾组织Drp1、p-Drp1 Ser637、细胞色素c(Cyt-c)、cleaved caspase-3表达,透射电镜下观察细胞线粒体超微结构。结果与S组比较,HI/R组和P组血清BUN和Cr浓度、肾组织细胞凋亡指数升高,p-Drp1 Ser637表达下调,Cyt-c、cleaved caspase-3表达上调(P<0.05),电镜下部分线粒体肿胀并出现空泡变性,线粒体嵴排列不规律或断裂变短;与HI/R组比较,P组血清BUN和Cr浓度、肾组织细胞凋亡指数降低,p-Drp1 Ser637表达上调,Cyy-c、cleaved caspase-3表达下调(P<0.05),线粒体超微结构明显改善。3组肾组织Drp1表达差异无统计学意义(P>0.05)。结论异丙酚预先给药减轻肝缺血再灌注小鼠肾损伤的机制与抑制Drpl Ser637去磷酸化有关。
Objective To evaluate the effect of propofol pretreatment on dephosphorylation of phospho-dynamin-related protein 1(p-Drp1)Ser637 during kidney injury induced by hepatic ischemia-reperfusion(I/R)in mice. Methods Thirty healthy SPF male C57 mice, weighing 20-25 g, were divided into 3 groups(n=10 each)using a random number table method: sham operation group(group S), hepatic I/R group(group HI/R)and propofol pretreatment group(group P). Hepatic I/R was produced by occluding the blood supply to the left lateral and median lobes of liver for 60 min followed by reperfusion in anesthetized mice.In group P, 1% propofol 30 mg/kg was intraperitoneally injected at 30 min before operation, while the equal volume of normal saline was given instead in S and HI/R groups.Blood samples were collected from the left ventricle at 6 h of reperfusion for determination of the concentrations of serum blood urea nitrogen(BUN)and creatinine(Cr). Renal tissues were obtained for determination of cell apoptosis(by TUNEL)and expression of Drp1, p-Drp1 Ser637, cytochrome-c(Cyt-c)and cleaved caspase-3(by Western blot)and for examination of the ultrastructure of mitochondria(by transmission electron microscopy). Apoptosis index was calculated. Results Compared with group S, the serum BUN and Cr concentrations and apoptosis index were significantly increased, the expression of p-Drp1 Ser637 was down-regulated, and the expression of Cyt-c and cleaved caspase-3 was up-regulated(P<0.05), and microscopic examination showed that mitochondria was swollen with vacuolization and mitochondrial cristae was irregularly distributed or disrupted and shortened in HI/R and P groups.Compared with group HI/R, serum BUN and Cr concentrations and apoptosis index were significantly decreased, the expression of p-Drp1 Ser637 was up-regulated, the expression of Cyt c and cleaved caspase-3 was down-regulated(P<0.05), and the ultrastructure of mitochondria was markedly improved in group P. There was no significant difference in the expression of Drp1 in renal issues be
作者
于向洋
贾莉莉
喻文立
杜洪印
Yu Xiangyang;Jia Lili;Yu Wenli;Du Hongyin(Tianjin Medical University First Center Clinical College, Tianjin 300192, China;Department of Anesthesiology, Tianjin First Center Hospital, Tianjin 300192, China)
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2019年第1期113-116,共4页
Chinese Journal of Anesthesiology
基金
天津市卫生行业重点攻关项目(16KG101)
天津市卫生和计划生育委员会中医中西医结合科研课题(2017056).
