新生大鼠缺氧缺血性脑病模型中己酮可可碱的干预作用研究

Study on effects of pentoxifylline on newborn rats models with hypoxic-ischemic brain damage

目的观察不同时间给予己酮可可碱(pentoxifylline,PTX)对新生大鼠缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)模型的影响。方法建立新生大鼠HIBD模型,120只出生7 d的wistar大鼠随机分为假手术(Sham)组、HIBD模型组和3种PTX(50 mg／kg腹腔注射)给药组,即缺血末均给药(I+PTX)组、缺氧末给药(H+PTX)组及缺血和缺氧末均给药(I,H+PTX)组,各组均于缺血缺氧处理后72 h取出左脑,测定脑组织水含量、大脑皮层神经组织游离钙离子浓度、超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮合酶(NOS)及一氧化氮(NO)。结果HIBD模型组与Sham组相比,脑组织含水量、游离钙离子浓度、MDA、NOS及NO水平显著升高(均P＜0.01),SOD水平明显降低(P＜0.01)。3种PTX给药组与HIBD模型组相比,脑组织含水量、游离钙离子浓度、MDA、NOS及NO水平均显著降低(均P＜0.01),SOD水平明显升高(P＜0.01)。以上作用尤以(I,H+PTX)组明显。结论 PTX对新生大鼠缺氧缺血后脑组织有保护作用,其机制可能与PTX改善能量代谢及减少局部细胞毒性物质有关。

Objective To observe the effects of pentoxifylline （PTX） treated at different time on newborn rats with hypoxic-ischemic brain damage （HIBD）. Methods Model of 7-day-old newborn Wistar rats with HIBD was established and 120 rats were randomly divided into sham operation group, HIBD model group, treated with PTX （50 mg/kg ip） post ischemic procedure （ I ＋ PTX） group, treated post hypoxie procedure （ H ＋ PTX） group and treated lost both period （ I, H ＋ PTX） group. Seventytwo h after hypoxic-ischemic operation, the left side brain was taken out and in that water contents, intracellular calcium, MDA, NOS and NO and the activity of SOD were measured. Results The water, content calcium, MDA, NOS and NO were markedly increased compared with sham operation group （P 〈0, 01 ）, while the activity of SOD were reduced significantly in HIBD model group （P 〈0. 01 ）. All three groups treated with PTX had lower water contents, calcium, MDA, NOS and NO, and higher activity of SOD （P 〈 0.01 ）, especially in （ I, H ＋ PTX） group. Conclusions PTX could protect brain of neonatal rat against HIBD, which might be the result of the improvement of energy metabolism and the removel of focal cvtotoxic substence.