HIF-1α对大鼠缺血-再灌注后Fas蛋白表达的影响  

Effects of hypoxia-inducible factor-1α on the expression of Fas protein after ischemia-reperfusion injury

作　　者：沈晓明[1] 金成[1] 张培建[2] 吕国强[1] 顾元龙[1] 

机构地区：[1]无锡市第三人民医院消化外科,214041 [2]扬州大学医学院外科教研室

出　　处：《江苏医药》2010年第19期2293-2295,共3页Jiangsu Medical Journal

基　　金：江苏省卫生厅科研课题(H200770);无锡三院青年基金资助项目(SYQNJJ09004)

摘　　要：目的探讨低氧预适应(HP)作用后的低氧诱导因子1α(HIF-1α)对大鼠缺血-再灌注损伤(I-RI)时Fas蛋白表达的影响及其意义。方法采用改良的自体肝移植模型研究I-RI。将SD大鼠随机分为正常对照(NC)、自体移植(AT)和HP三组,每组24只。HP组术前用8%氮氧混合气体处理90min,分别于术后1、6、24h处死大鼠取肝脏标本,抽血检测肝功能,采用免疫组化方法测定HIF-1α及Fas蛋白的表达,并在透射电镜下比较超微结构的改变。结果 NC组HIF-1α表达最弱,HP组与AT组相比较,HP组各时相点表达更明显。经图像处理转化为平均灰度值后,与NC组比较,HP和AT两组各时相表达增强(P<0.05),其中HP组HIF-1α的表达更强(P<0.05);HP组各时段的Fas蛋白表达均明显低于AT和NC组(P<0.05);HP组血清ALT和AST水平显著低于AT组(P<0.05);AT组镜下见肝细胞浓缩,细胞间隙变大,染色质粗糙,核仁浓缩甚至裂解,细胞器明显密集化,线粒体肿胀,膜模糊不清;而HP组肝细胞形态明显改善,仅部分细胞器如线粒体出现轻度肿胀。结论 HIF-lα可在HP的作用下高表达,从而下调肝组织中Fas蛋白含量,减轻肝脏I-RI。Objective To explore the effects of hypoxia-inducible factor-1a（HIF-1α） on the expression of Fas protein after ischemia-reperfusion injury（I-RI）. Methods A modified orthopotic liver autotransplantation model was used to simulate I-RI.SD rats were randomly divided into three groups of normal control （group NC）,autotransplantation （group AT） and hypoxia preconditioning（HP）（group HP） with 24 rats each.Group HP was given 8% oxygen atmosphere for 90 minutes before operation. At 1,6,and 24 hours after operation,the rats were killed.The liver tissue was sampled for detecting the expressions of Fas and HIF-1α.Blood was drawn for conducting a chemical examination.The morphology of hepatocytes was observed under transmission electron microscopy（TEM）.Results Serum levels of ALT and AST at 1,6 and 24 hours were lower in group HP than those in group AT （P0.05）. The expression of HIF-1α was increased significantly （P0.05） in group HP at each measurement point.The expression of Fas protein was decreased significantly in group HP（P0.05）. The swollen of hepatic tissues under TEM was less in group HP than that in group AT.Conclusion With HP,HIF-1α is higherly expressed,which down-regulates the expression of Fas protein and attenuates I-RI.

关 键 词：低氧诱导因子1Α 低氧预适应 FAS蛋白 缺血-再灌注损伤 

分 类 号：R562[医药卫生—呼吸系统]