克霉唑抗肝缺血-再灌注损伤凋亡机制的研究  

Study of Clotrimazole on Cell Apoptosis in Rat Liver After Ischemia-reperfusion Injury

作　　者：许静[1] 陈杰[2] 罗子玲[1] 官碧琼[1] 何炳洪[1] 孙萍萍[2] 袁芳[3] 

机构地区：[1]南方医科大学附属第三医院药剂科,广州510630 [2]中山大学附属第一医院药学部,广州510080 [3]广东药学院药科学院药理系,广州510006

出　　处：《医药导报》2015年第4期432-435,共4页Herald of Medicine

基　　金：国家自然科学基金资助项目(30972917);广东省医学科研基金资助项目(A2013193);广东省药学会肝炎用药研究基金资助项目(2011G25)

摘　　要：目的观察孕烷X受体(PXR)诱导药克霉唑对肝脏缺血-再灌注损伤后肝细胞凋亡影响,并探讨其机制。方法建立大鼠肝脏缺血-再灌注模型,32只雄性SD大鼠随机分为假手术组,模型对照组和克霉唑小剂量组、大剂量组进行肝缺血-再灌注损伤。TUNEL法检测肝组织中凋亡细胞,Western blot检测肝脏CYP3A1、Bcl-2、Bax、PARP表达水平。结果克霉唑小剂量组、大剂量组与模型对照组比较,细胞凋亡数减少,组织损伤减轻,凋亡细胞百分率明显降低,Bcl-2/Bax比值明显升高,抑制PARP剪切,提示有较好的抗凋亡作用,均差异有统计学意义;作为PXR特异性强诱导药克霉唑,与假手术组比,能明显诱导CYP3A1基因表达。结论 PXR特异性强诱导药克霉唑可能通过促进Bcl-2表达及抑制Bax表达而拮抗肝细胞凋亡,从而减轻肝脏缺血-再灌注损伤,也与抑制PARP剪切有关。Objective To investigate the effect of clotrimazole on apoptosis of hepatic cells after ischemia-reperfusion injury and its mechanism. Methods Hepatic ischemia-reperfusion rat model was established. Thirty-two male Sprague-Dawley rats were randomly allocated into sham-operated group, model control group, low dose clotrimazole group and high dose clotrimazole group. Apoptosis in hepatic tissue was assessed by TUNEL method. Protein expression levels of CYP3A1,Bcl-2,Bax and PARP were measured by Western blotting. Results As compared with model control group, the apoptosis rate, tissue injury,activity of plasma enzymes and the Bax/Bcl-2 expression ratio were reduced in low and high dose clotrimazole groups. The apoptotic index in both clotrimazole-treated groups was lower than that of model control group with statistically significant difference. CYP3A1 expression was significantly induced by clotrimazole compared to the sham-operated group. Conclusion Clotrimazole may inhibit apoptosis of hepatic cells by up-regulating Bcl-2 and down-regulating Bax, thus produce a protective effect on hepatic ischemia-reperfusion injury and it is also related to the inhibition of PARP shear.

关 键 词：克霉唑 肝细胞 损伤 缺血-再灌注 细胞凋亡 孕烷X受体 

分 类 号：R977.3[医药卫生—药品] R575[医药卫生—药学]