Protective effects of N-acetylcysteine regulating HIF-1a / iNOS signal pathway on ischemic-reperfusion injury in rat heart transplantation
10.3760/cma.j.issn.1008-6315.2018.03.012
- VernacularTitle: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
- Author:
Xue YI
1
;
Yongqian LIU
;
Hanqiao LI
;
Lunhua CHEN
;
Hongyuan ZHONG
;
Yigen WU
;
Lixian CHENG
;
Ying SHI
;
Zhanqing LI
Author Information
1. 361023,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
- Keywords:
N-acetylcysteine;
Heart transplautation;
Ischemia-reperfusion injury(IRI);
Hypoxia inducible factor 1a(HIF-1a);
Inducible nitric oxide synthase (iNOS)
- From:
Clinical Medicine of China
2018;34(3):249-252
- CountryChina
- Language:Chinese
-
Abstract:
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.Methods Eighty 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.Results HIF-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).Conclusion HIF-1a/iNOS signaling pathway can regulate ischemia reperfusion injury in rat heart transplantation,and the protective effect of NAC on donor heart maybe mediated via this pathway.