N-乙酰半胱氨酸提高大鼠心脏移植的供心存活时间研究

Research on N-acetylcysteine prolonging survival duration of donor heart after heart transplantation in rats

目的观察N-乙酰半胱氨酸(N-acetylcysteine,NAC)预处理对心脏移植缺血再灌注损伤(ischemiareperfusion injury,IRI)的保护作用。方法健康雄性Lewis大鼠80只和BN大鼠20只,按数字表法随机分为3组。对照组:摘取供体心脏前30 min或移植前30 min经下腔静脉注射0.9%氯化钠溶液2 m L;供体预处理组:摘取供心前30 min经下腔静脉注射NAC 300 mg/kg,受体不处理;受体预处理组:受体于移植前30 min经下腔静脉注射NAC 300 mg/kg,供体不处理。供心冷藏于4℃HTK(histidine-tryptophan-ketoglutarate)液18 h后建立大鼠腹腔异位心脏移植模型(Lewis→Lewis)。使用Kaplan-Meier分析其生存率(BN→Lewis);分别于移植后24 h取移植物检测过氧化脂质(lactoperoxidase,LPO)和超氧化物歧化酶(superoxide dismutase,SOD)活性。结果 NAC预处理组大鼠生存率明显高于对照组,差异有统计学意义(P<0.05)。移植后24 h供心心肌组织中SOD浓度较对照组高,差异有统计学意义[(4.71±1.09)U/m L vs.(2.38±0.39)U/m L,P<0.05];两组LPO浓度比较,差异无统计学意义(P>0.05)。供体预处理组与受体预处理心肌组织中LPO、SOD浓度比较,差异无统计学意义(P>0.05)。结论在大鼠心脏移植中NAC通过直接抗氧化及提高氧化酶活性减轻了供心IRI,提高了供心的存活率。

Objectives To explore the protective effect of N-acetylcysteine（NAC） on ischemia-reperfusion injury（IRI） during heart transplantation in rats. Methods Totally 80 healthy male Lewis rats and 20 healthy male BN rats were randomly divided into three groups. Control group ： 2 m L of saline was infused via inferior vena cava 30 min before donor harvest; Donor preconditioning group ： NAC（300 mg / kg BW; iv.） was infused via inferior vena cava 30 min before donor harvest, but no treatment in recipient; Recipient preconditioning group ： NAC（300 mg / kg BW; iv.） was infused via inferior vena cava 30 min before recipient implantation, but no treatment in donor. Grafts underwent cold storage in 4℃ conventional HTK（histidine-tryptophan-ketoglutarate） solution for 18 h prior to heterotopic transplantation（Lewis →Lewis）. Another 20 male Lewis rates for recipients, 20 male BN rates for donor were used for survival. Graft function was monitored by daily palpation. Graft lactoperoxidase（LPO） and superoxide dismutase（SOD）activity were detected 24 h after reperfusion. Results Survival rate of rats in NAC pretreatment group was significantly higher than that in control group（P〈0.05）. SOD activity in donor preconditioning group was significantly higher than that in control group 24 h after reperfusion [（4.71 ±1.09） U / m L vs.（2.38 ±0.39） U / m L, P〈0.05 ]; but LPO activity of the two groups had no significant difference（P〉0.05）. LPO activity and SOD activity between donor preconditioning group and recipient preconditioning group had no significant difference（P〉0.05）. Conclusions NAC reduces IRI after heart transplantation and improves the outcome of the transplanted heart after prolonged cold preservation, which is most likely through anti-oxidative and anti-apoptotic mechanisms.