CAJ | 학술논문

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。
목적：관찰잉완X수체( PXR)유도약극매서대간장결혈-재관주손상후간세포조망영향,병탐토기궤제。방법건립대서간장결혈-재관주모형,32지웅성SD대서수궤분위가수술조,모형대조조화극매서소제량조、대제량조진행간결혈-재관주손상。 TUNEL법검측간조직중조망세포,Western blot검측간장CYP3A1、Bcl-2、Bax、PARP표체수평。결과극매서소제량조、대제량조여모형대조조비교,세포조망수감소,조직손상감경,조망세포백분솔명현강저,Bcl-2/Bax비치명현승고,억제PARP전절,제시유교호적항조망작용,균차이유통계학의의；작위PXR특이성강유도약극매서,여가수술조비,능명현유도CYP3A1기인표체。결론 PXR특이성강유도약극매서가능통과촉진Bcl-2표체급억제Bax표체이길항간세포조망,종이감경간장결혈-재관주손상,야여억제PARP전절유관。
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.