左旋精氨酸/一氧化氮在鼠心移植心肌缺血再灌注损伤中的研究

The study of L-Arginine/Nitric oxide pathway on the mechanism of cardiac ishemia reperfusion injury in a heterotopic rat heart transplant model

关键词:  心肌缺血再灌注损伤  一氧化氮  左旋精氨酸  髓质过氧化酶(MPO)  同种异体鼠心移植

Key words:  myocardial ischemia reperfusion injury,L-Arginine  Nitric Oxide  MPO  the heterotopic rat cardiac transplantation

摘要:

实验通过同种异体鼠心移植模型研究一氧化氮(NO)体内合成前体左旋精氨酸(L-Arg)及一氧化氮合成酶抑制剂(L-NAME)(N-L-精氨酸甲硝基酯)在心肌缺血再灌注过程中对心肌丙二醛(MDA)，髓质过氧化酶(MPO)及能量代谢指标ATP、CP的影响。实验分四组，组Ⅰ：空白对照组(n＝10)，组Ⅱ：L-Arg组(n＝10)，组Ⅲ：L-NAME组(n＝10)，组Ⅳ：L-Arg＋L-NAME组(n＝10)。组Ⅰ受体、供体均经颈外静脉输入生理盐水，供心灌注冷心脏停跳液(0～4℃改良St THOMAS液)，其余各组均分别于生理盐水、心脏停搏液及心脏保存液中加L-Arg(3 mmol/L)、L-NAME(100μmol/L)、L-Arg(3 mmol/L)＋L-NAME(100 μmol/L)。结果表明：L-Arg能明显降低再灌注损伤心肌中的MDA(P＜0.001)，降低中性粒细胞聚集浸润的标志酶MPO含量(P＜0.05)，使ATP、CP升高(P＜0.05)；而L-NAME使心肌中MDA含量较对照组显著升高(P＜0.05)，而ATP、CP含量显著下降(P＜0.05)。

Abstract:

Aim:Myocardial ischemia reperfusion may result in coronary endotheilal dysfunction and reduce endogenous releasing of nitric oxide synthesizde by the vascular endothelium.The effects of nitric oxide precursor L-Arginine on anti-ischemia reperfusion injury and endothelial protection as well as the injury mechanism of nitric oxide inhibitor Nw-nitro-L-methy Ester were investigated in the heterotopic rat cardiac transplantations. Method:80 SD rats, which were pretreated with different kinds of drug viaextra jugular vein one hour before operation, were randomly divided into 4 groups,Group Ⅰ: Control grorp(n＝10)，Group Ⅱ:L-Arginine group(n＝10)， Group Ⅲ：L-NAME group(n＝10)，Group Ⅳ：L-Arginine plus L-NAME group(n＝10)， After the heterotopic rat cardiac transplantations,the hearts,following 60 min ischemia and 40min reperfusion, were excised and immersed immediately into liquid mitrogen for assays of ATP、CP、MDA(Malondialdehyde)、MPO(Myeloperoxidase).Result: The content of MDA and MPO(an identification enzyme for PMN accumulation and adhererce)in L-Arginine group was significantly decreased(P＜0.05). Myocardial content of ATP and CP were also improved significantly(P＜0.05). In contrast,MDA content in L-NAME group was significantly highr than control group and L-Arginine group(P＜0.05). Although the MPO content in L-NAME group was significantly higher than L-Arginine group, there was no significant difference between L-NAME and control group.L-Arginine plus L-NAME group versus control group showed no significant difference on MDA、MOP、ATP and CP.Conclusion：The outcome of experiment suggests that L-Arginine attenuate reperfusion myocardium and coronary endothelium injury caused by oxygen free radicals, inhibite the PMN aggregation and adherenc,preserve the endothelial function, relax coronary vessels and ameliorate ATP、CP anabolism.Nevertheless,L-NAME escalated the ischemia-reperfusion injury by blocking NO synthesis, which can be reversed by L-Aiginine