CAJ | 학술논문

目的评价瑞芬太尼预处理对肝硬化大鼠肝缺血再灌注损伤的影响.方法健康雄性SD大鼠,体重160～ 180 g,采用40％四氯化碳花生油溶液3 ml/kg灌胃,每周2次,共8周,建立大鼠肝硬化模型.灌胃结束后2周时,取肝硬化大鼠35只,采用随机数字表法,将其分为5组(n=7):假手术组(S组)、缺血再灌注组(I/R组)和不同剂量瑞芬太尼预处理组(R1组、R2组和R3组).采用结扎肝动脉、门静脉和胆管分支30 min,再灌注90 min的方法制备肝硬化大鼠肝缺血再灌注损伤模型.R1组、R2组和R组分别以0.4、2.0和10.0μg·kg-1·min-1的速率静脉输注瑞芬太尼15 min,停止输注10min后,缺血30 min,再灌注90 min.再灌注90 min时,抽取腹主动脉血样,测定血清ALT和AST的活性;然后处死大鼠,取肝组织,测定SOD活性、MDA含量和细胞凋亡指数,分别采用Western blot法和免疫组化法测定活化的caspase-3表达.结果与S组比较,I/R组、R1组、R2组和R3组血清ALT和AST的活性、肝组织MDA含量和细胞凋亡指数升高,肝组织SOD活性降低,活化的caspase-3表达上调(P＜0.01);与I/R组比较,R1组上述各指标差异无统计学意义(P＞0.05),R2组和R3组血清ALT和AST的活性、肝组织MDA含量和细胞凋亡指数降低,肝组织SOD活性升高,活化的caspase-3表达下调(P＜0.01).结论瑞芬太尼预处理可减轻肝硬化大鼠肝缺血再灌注损伤,其机制与抑制脂质过氧化反应和细胞凋亡有关.
목적 평개서분태니예처리대간경화대서간결혈재관주손상적영향.방법 건강웅성SD대서,체중160～ 180 g,채용40％사록화탄화생유용액3 ml/kg관위,매주2차,공8주,건립대서간경화모형.관위결속후2주시,취간경화대서35지,채용수궤수자표법,장기분위5조(n=7):가수술조(S조)、결혈재관주조(I/R조)화불동제량서분태니예처리조(R1조、R2조화R3조).채용결찰간동맥、문정맥화담관분지30 min,재관주90 min적방법제비간경화대서간결혈재관주손상모형.R1조、R2조화R조분별이0.4、2.0화10.0μg·kg-1·min-1적속솔정맥수주서분태니15 min,정지수주10min후,결혈30 min,재관주90 min.재관주90 min시,추취복주동맥혈양,측정혈청ALT화AST적활성;연후처사대서,취간조직,측정SOD활성、MDA함량화세포조망지수,분별채용Western blot법화면역조화법측정활화적caspase-3표체.결과 여S조비교,I/R조、R1조、R2조화R3조혈청ALT화AST적활성、간조직MDA함량화세포조망지수승고,간조직SOD활성강저,활화적caspase-3표체상조(P＜0.01);여I/R조비교,R1조상술각지표차이무통계학의의(P＞0.05),R2조화R3조혈청ALT화AST적활성、간조직MDA함량화세포조망지수강저,간조직SOD활성승고,활화적caspase-3표체하조(P＜0.01).결론 서분태니예처리가감경간경화대서간결혈재관주손상,기궤제여억제지질과양화반응화세포조망유관.
Objective To evaluate the effect of remifentanil preconditioning on hepatic ischemiarepeffusion (I/R) injury in rats with liver cirrhosis.Methods Healthy male Sprague-Dawley rats,weighing 160180 g,received 40％ tetrachloride carbon 3 ml/kg (in peanut oil) intragastrically twice a week for 8 weeks to induce liver cirrhosis.Thirty-five rats with liver cirrhosis were randomly divided into 5 groups (n =7 each) using a random number table:sham operation group (group S),group I/R,and preconditioning with different does of remifentanil groups (R1,R2 and R3 groups).Hepatic I/R injury was induced by clamping the branches of hepatic artery,portal vein and common bile duct in the left and median hepatic lobes for 30 min followed by 90 min reperfusion in anesthetized rats with liver cirrhosis.In R1,R2 and R3 groups,remifentanil was infused intravenously at 0.4,2.0 and 10.0 μg· kg-1· min-1 for 15 min,respectively,and the rats were exposed to ischemia for 30 min followed by 30 reperfusion starting from 10 min after infusion was stopped.At 90 min of reperfusion,blood samples were collected from the abdominal aorta for determination of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities.The rats were then sacrificed and livers were removed for determination of superoxide dismutase (SOD) activity,malondialdehyde (MDA) content,and expression of activated caspase-3 (using immunohistochemistry and Western blot analysis) and for detection of cell apoptosis in hepatic tissues.Apoptotic index was calculated.Results Compared with group S,the serum ALT and AST activities,MDA content and apoptotic index were significantly increased,SOD activity was decreased,and the expression of activated caspase-3 was up-regulated in I/R,R1,R2 and R3 groups.Compared with group I/R,no significant changes were found in the indexes mentioned above in group I/R,and the serum ALT and AST activities,MDA coment and apoptotic index were significantly decreased,SOD activity was increased,and the expression of activated caspase-3 was down-regulated in R2 and R3 groups.Conclusion Remifentanil preconditioning can reduce hepatic I/R injury in rats with liver cirrhosis,and the mechanism is related to inhibition of the lipid peroxidation and cell apoptosis.