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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
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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StTHOMAS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 ( 3mmol/L)、L -NAME ( 10 0 μmol/L)、L -Arg ( 3mmol/L) +L -NAME ( 10 0 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 0 0 1) ,降低中性粒细胞聚集浸润的标志酶MPO含量 (P <0 0 5) ,使ATP、CP升高 (P <0 0 5) ;而L -NAME使心肌中MDA含量较对照组显著升高 (P <0 0 5) ,而ATP、CP含量显著下降 (P <0 0 5)。 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 40 min 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.
出处 《大连医科大学学报》 CAS 2000年第3期168-170,177,共4页 Journal of Dalian Medical University
关键词 心肌缺血 再灌注损伤 一氧化氮 左旋精氨酸 MPO myocardial ischemia reperfusion injury L-Arginine Nitric Oxide MPO the heterotopic rat cardiac transplantation.
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