N-乙酰半胱氨酸预处理在大鼠心脏移植供心冷缺血再灌注损伤时对HIF-1α的影响

EFFECTS OF N-ACETYLCYSTEINE ON HYPOXIA-INDUCIBLE FACTOR-1 ALPHA IN MYOCARDIAL COLD ISCHEMIA REPERFUSION INJURY OF RATS HEART TRANSPLANTATION

目的观察在大鼠心脏移植(HTx)时N-乙酰半胱氨酸(NAC)预处理对供心心肌缺血再灌注后心肌低氧诱导因子1(HIF-1)的影响并探讨其可能的机制。方法健康雄性Lewis大鼠,每组10只,随机分为三组:对照组:取供体心脏或移植前30min,经供体心脏或受体大鼠腔静脉注入0.9%盐水0.3ml;供体预处理组:供体鼠获取其心脏前30min,腔静脉注入NAC300mg/(kg·w),受体鼠不处理;受体预处理组:受体鼠在移植前30min,经腔静脉注入NAC300mg/(kg·w),供体大鼠不处理。将冷藏在4℃HTK液18h供心移植于受体大鼠腹腔建立同种异体异位心脏移植模型。免疫组化检测HIF-1α蛋白表达,Real time-PCR检测HIF-1αmRNA表达。结果 HIF-1α蛋白表达NAC供、受体预处理组均低于对照组(3.38.±0.18 vs2.7±0.15,2.2±0.20,P<0.05);HIF-1αmRNA表达,NAC供、受体预处理组与对照组比较钧无统计学差异(P>0.05)。结论 NAC可能通过抑制HIF-1α通路减轻大鼠心脏移植IRI来保护供心。

Objective To study the influence of N-acetylcysteine（NAC）on Hypoxia-inducible factor1 alpha（HIF-1α）during ischemia reperfusion injury of donor heart in rats＇ heart transplantation,and the possible mechanism of N-acetylcysteine.Methods Eighty male Lewis rats were randomly divided into 3 groups.Control group：0.3 ml saline was infused by vena cava 30 min before donor heart harvest or implantation;don＇t pretreatment group.NAC（300 mg/kg.w）was infused by inferior vena cava 30 min before donor heart harvest,receptor donor be treated;and recipient pretreatment group：NAC（300 mg/kg.w）was infused via inferior vena cava of recipient rats 30 min before donor heart implantation,donor don＇t be processed.Grafts underwent cold storage in 4℃ conventional Histidine Tryptophan Ketoglutarate（HTK）solution for 18 hrs prior to heterotopic transplantation.Rat heterotopic heart transplantation model was established.HIF-1αmRNA and protein expression were detected by real time PCR and immunohistochemistry.Results HIF-1αprotein expression was significantly lower in NAC donor pretreatment and recipient pretreatment group compared with control group（2.7±0.15,2.2±0.20 vs.3.38.±0.18,P〈0.05）.HIF-1αmRNA was no significant between NAC pretreatment group and control group（P〉0.05）.Conclusion N-acetylcysteine relieves ischemia reperfusion injury of rats＇ heart transplantation through reducing expression of HIF-1αexpression,which has a protective effect on donor heart myocardial cell.