内皮素-1在大鼠肢体缺血再灌注致脑损伤中的作用及BQ123的保护效应

The role of ET-1 in the brain injury after hind limbs ischemia-reperfusion in rats and the protective effect of BQ123

①目的探讨内皮素A(ETA)受体拮抗剂BQ123对其病理过程的保护机制。②方法实验用W istar大鼠,随机分为8组:对照组,缺血组(I),缺血再灌组(IR):包括IR 0.5、IR2、IR4、IR6、IR10小时5组,BQ123+IR4小时组。分别测定各组动物血浆内皮素-1(ET-1)、丙二醛(MDA)、黄嘌呤氧化酶(XOD)、超氧化物歧化酶(SOD)、乳酸脱氢酶(LDH)、肌酸磷酸激酶(CK)及脑组织ET-1、MDA、XOD、SOD、髓过氧化物酶(MPO)的变化。③结果LIR后血浆及脑组织ET-1含量增加,在IR4小时组达到最高,以后有所下降。脂质过氧化物MDA及LDH、CK和组织MPO增加,SOD活性降低,ET-1变化趋势能较好地反映组织的损伤性变化。给予ETA受体阻断剂BQ123后,血浆及脑组织中ET-1水平均下降,脑损伤减轻。④结论LIR后ET-1的增加可能是导致脑损伤发生重要因素,应用BQ123阻断其作用,可有效地减轻LIR所致的脑损伤。

Objective To evaluate the possible role of endothelin - 1 in the development of brain injury after hind limbs ischemia - reperfusion （LIR） , and the protective mechanisms of ETA receptor antagonist BQ123 on its pathologic process. Methods Wistar rats were divided into 8 goups ： Control group, ischemia group（ I）, ischemia - reperfusion group （IR） including five groups ： IR 0.5h,IR2h,IR4h,IR6h,IR10h and BQ123 ＋ IR4h group. The changes of Endothelin - 1 （ ET - 1 ） .malondialdehyde （ MDA）, xanthine oxidase （ XOD ）, superoxide dismutase （ SOD ）, actate dehydrogenase （LDH） and creatine kinase （CK） in plasma were observed. The content of ET - 1 ,MDA.XOD.SOD,myelopeerxidase（MPO） in the brain tissue were detected. Results The content of ET - 1 in plasma and brain tissue increased following LIR, which were maxium in IR4h,then decreased. The content of MDA, XOD, LDH, CK and tissue MPO also increased, the activation of SOD decreased. The levels of ET - 1 reflected the changes of brain injury. After using ETA receptor antagonist BQ123 ,the content of ET - 1 in plasma and brain tissue decreased, brain injury lightened. Conclusion The increase of ET - 1 after LIR might be the main factor of causing brain injury. Using BQ123 could lighten brain injury effectively.