去铁胺在大鼠自体肝移植术后余肝细胞凋亡中的作用

目的 探讨去铁胺预处理对大鼠自体肝移植余肝细胞凋亡的作用及机制.方法 建立大鼠自体肝移植模型,将96只健康雄性SD大鼠随机分为去铁胺预处理(D组)32只,注射用水对照组(C组)32只和假手术模型(S组)32只.分别于术后0.5、2、6、24 h各时间点处死大鼠,检测血清ALT和AST水平;做病理组织学检查,免疫组织化学检测缺氧诱导因子(HIF)-1α、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1及bcl-2蛋白的表达,TUNEL测定细胞凋亡.结果 在各个时间点,D组血清ALT及AST水平及IL-1、TNF-α蛋白表达量和凋亡指数明显低于C组(P<0.01),而HIF-1α和bcl-2蛋白表达量明显高于C组(P<0.01).结论 去铁胺预处理对大鼠自体肝移植余肝细胞凋亡具有保护作用,其作用机制部分可能与促进HIF-1α表达上调,从而降低炎性因子水平,促进bcl-2表达达到抑制细胞凋亡的作用.

The role of deferoxamine pretreatment in hepatic cell apoptosis of residual liver following autotransplantation in rats

Objective To investigate the role of deferoxamine pretreatment in hepatic cell apoptosis of residual liver following liver auto-transplantation in rats.Methods The liver auto-transplantation model in rats was established.Ninety-six male Sprague-Dawley rats were randomly divided into 3 groups: 32 rats in deferoxamine pretreatment group (D) ,32 rats in control group with aqua pro injection pretreatment (C) ,and 32 rats in sham-operated group (S).The animals were killed at 30 min,2,6 and 24 h after operation respectively.The levels of serum ALT and AST were determined.Liver histological changes were observed by HE staining.Apoptosis was assayed by TUNEL.The protein expression of HIF-1α,TNF-α, IL-l and bcl-2 was detected by immunohistochemistry.Results At 30 min,2,6 and 24 h after operation,the levels of ALT and AST, apoptosis index, and the expression levels of IL-1 and TNF-α proteins were significandy higher in group C than in group D (P <0.01) ,but the expression levels of HE-1α and bcl-2 were higher in group D than in group C.Conclusion Deferoxamine pretreatment protects hepatic cells from apoptosis of residual liver following liver auto-transplantation in rats by up-regulating the HIF-1α expression, decreasing levels of TNF-α and IL-1, and promoting the expression of bcl-2.