一氧化氮、内皮素-1对大鼠肢体缺血/再灌注后脑损伤的影响

THE EFFECT OF NO, ET-1 ON BRAIN INJURY AFTER HIND LIMBS ISCHEMIA/REPERFUSION IN RATS

目的 :研究一氧化氮 (NO)和内皮素 1(ET 1)在大鼠肢体缺血 /再灌注 (LI/R)后脑损伤中的作用 ,探讨NO/ET 1平衡关系的变化对脑损伤的影响。方法 :在大鼠LI/R损伤模型上 ,应用NO合成前体物质L 精氨酸 (L Arg)、一氧化氮合酶 (NOS)抑制剂氨基胍 (AG)、ETA 受体阻断剂BQl2 3进行干预 ,观察血浆NO、ET 1、MDA、XOD、SOD、LDH及脑组织tNOS、iNOS、cNOS、NO、ET 1、MDA、XOD、MPO、SOD的变化。结果 :与对照组比较 ,I/R组血浆MDA、XOD、LDH及脑组织MDA、XOD、MPO升高 ,SOD活性降低 (P <0 .0 1) ,脑组织tNOS和iNOS明显升高 ,而cNOS明显降低 (P <0 .0 1) ,I/R组血浆及脑组织NO、ET 1增加 ,NO/ET 1比值降低 ,脑损伤加重。应用L Arg及BQ12 3后 ,血浆及脑组织NO/ET 1比值较I/R组升高 ,脑损伤减轻 ,应用AG后 ,NO/ET 1比值降低 ,脑损伤进一步加重。结论 :肢体缺血 /再灌注后 ,一氧化氮与内皮素 l的比值降低时脑损伤加重。

Aim: To study the roles of nitric oxide(NO) and ET-1 in brain injury after hind limbs ischemia/reperfusion in rats and to investigate the effect of NO/ ET-1 balance on brain injury. Methods: On a model of the hind limbs ischemia/reperfusion(LI/R) of rats, we used L-Arg(L-arginine,L-Arg), one of the substrates in the process of nitric oxide, aminoguanidine(AG) which inhibits nitric oxide synthase(NOS) and ET A receptor antagonist BQ123, to observe the changes of NO, ET-1, MDA, XOD, SOD, LDH in plasma and tNOS, iNOS, cNOS, NO, ET-1, MDA, XOD, MPO, SOD in brain tissue. Results: Compared with the control group, the content of MDA, XOD, LDH in plasma and MDA, XOD, MPO in brain tissue increased. The activity of SOD decreased(P< 0.01 ). The content of tNOS, iNOS in brain tissue increased, cNOS decreased(P<0.01).The content of NO, ET-1 in I/R group in plasma and brain tissue increased, the ratio of NO/ET-1 decreased. The brain injury was deteriorated. After using L-Arg and BQ123, the ratio of NO/ET-1 in plasma and brain tissue increased, the brain injury lightened. Whereas after using AG, the ratio of NO/ET-1 decreased,brain injury became more serious. Conclusion: The NO/ET-1 ratio decreased after LI/R, brain injury became more serious.