N-乙酰半胱氨酸调节低氧诱发因子1a／一氧化氮合酶信号通路对大鼠心脏移植缺血再灌注损伤的保护作用  

Protective effects of N-acetylcysteine regulating HIF-1a / iNOS signal pathway on ischemic-reperfusion injury in rat heart transplantation

作　　者：伊雪 刘永前 李涵乔 陈纶华 钟宏源 吴艺根 程丽宪 石莺 李占清 Yi Xue;Liu Yongqian;Li Hanqiao;Chen Lunhua;Zhong Hongyuan;Wu Yigen;Cheng Lixian;Shi Ying;Li Zhanqing(Department of Pathology and Pathophysiology, Xiamen Medical Collgege ,Xiamen 361023, China)

机构地区：[1]厦门医学院基础医学部病理与病理生理教研室机能与临床转化福建省高校重点实验室,361023 [2]厦门大学公共卫生学院 [3]厦门医学院附属第二医院心胸外科

出　　处：《中国综合临床》2018年第3期249-252,共4页Clinical Medicine of China

基　　金：福建省自然科学基金项目（2016D014）,福建省厦门市科技惠民项目（3502220164057）

摘　　要：目的观察低氧诱发因子1a（hypoxia inducible factor 1a，HIF-1a）/一氧化氮合酶（iNOS）信号通路对大鼠心脏移植心肌缺血再灌注损伤的影响及N-乙酰半胱氨酸（N-acetylcysteine，NAC）对供心的保护作用的可能机制。方法同系Lewis雄性大鼠60只，随机分为3组，每组各20只：对照组：获取供体心脏或受体大鼠移植前30 min，经供体或受体大鼠腔静脉注射0.9%盐水0.3 ml；NAC供体预处理组：获取供体心脏前30 min经供体大鼠腔静脉注入NAC 300 mg/kg.w；NAC受体预处理组：移植前30 min经受体大鼠腔静脉注入NAC 300 mg/kg.w。建立移植模型，移植后24 h后获取移植物。免疫组织化学法和Real time-PCR法检测供心心肌组织的iNOS、HIF-1a蛋白和mRNA表达。结果移植物中HIF-1a蛋白表达供、受体NAC预处理组与对照组比较差异有统计学意义（2.72±0.17、2.24±0.23 、3.14.±0.16，F＝56.26，P＝0.000），且均低于对照组（P均〈0.05），iNOS蛋白表达供、受体NAC预处理组与对照组比较差异有统计学意义（1.52±0.18、1.61±0.19 、3.30± 0.18，F＝232.345，P＝0.000），且均低于对照组（P均〈0.05）；移植后24 h移植物心肌组织HIF-1a、iNOS mRNA供、受体NAC预处理组及对照组比较，差异均有统计学意义（F值分别为7.467、16.490，P值分别为0.003、0.000），且NAC受体预处理组iNOS mRNA表达较对照组明显降低（P〈0.05）。结论HIF-1a/iNOS信号通路可以调控大鼠心脏移植缺血再灌注损伤，NAC对供体心脏的保护作用可能通过此通路起作用。Objective To observe the effect of HIF-1a/iNOS signaling pathway on myocardial ischemia-reperfusion injury in rat heart transplantation and the protective mechanism of N- acetylcysteine （NAC） on donor heart after cardiac transplantation in rats.MethodsEighty healthy male Lewis rats were randomly divided into 3 groups, the control group （0.3 ml saline was infused via inferior vena cava 30 min before donor harvest or implantation）, NAC donor pretreatment group [NAC （30 mg/kg.w） was injected into the vena cava of donor rat 30 min defore donor harvest], and the NAC receptor pretreatment group（NAC 300 mg/kg.w was injected into the vena cava of the recipient rats 30 min before transplantation.The 30 min was injected into the vena cava of the recipient rats）. A transplant model was established and the graft was obtained after 24 h transplantation.The expression of iNOS, HIF-1a and mRNA in cardiac muscle tissue was detected by immunohistochemistry and Real time-PCR.ResultsHIF-1a protein expression in graft myocardial tissue was significantly lower in NAC donor pretreatment and recipient pretreatment group compared with control group （P〈0.05）, the differences were statistically significant （2.72±0.17 vs.2.24±0.23 vs.3.14.±0.16, F=56.26, P=0.000）. The iNOS protein expression in NAC donor pretreatment group, and NAC recipient pretreatment group were lower than that in the control group（1.52±0.18 vs.1.61±0.19 vs.3.30±0.18, F=232.345, P=0.000）, the differences were statistically significant（P〈0.05）.24 h after transplantation, the differences in graft myocardial tissue HIF-1a and iNOS mRNA among the three groups were statistically significant （F=7.467, 16.490, P=0.003, 0.000）. The expression of iNOS mRNA in the NAC receptor pretreatment group was significantly lower than that in the control group （P〈0.05）.ConclusionHIF-1a/iNOS signaling pathway can regulate ischemia reperfusion injury in rat heart transplantation, and the protective effect of NAC on donor heart maybe mediated

关 键 词：N-乙酰半胱氨酸 心脏移植 缺血再灌注损伤 低氧诱导因子1a 诱导型一氧化 氮合酶 

分 类 号：R654.2[医药卫生—外科学]