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.
出处
《医药导报》
CAS
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)
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
Clotrimazole
Hepatocytes
Injury,Ischemia-reperfusion
Apoptosis
Pregnane X receptor