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目的 观察己酮可可碱 (PTX)对沙鼠全脑缺血 /再灌注模型的作用效果 ,并对其作用机制进行初步探讨。方法 夹闭双侧颈动脉 ,诱导沙鼠全脑缺血 ,30分钟后松夹 ,再灌注 90min。在缺血诱导时 ,静脉给予 2 5mg·kg-1,或者 5 0mg·kg-1的PTX ;另一组于再灌注开始时静脉输注 2 5mg·kg-1的PTX。假手术组和对照组输入相同容积的 0 9%NaCl。再灌注开始时以 0 2 %伊文思兰 1ml·10 0g-1对所有沙鼠腹腔注射。实验结束时断头取脑 ,- 70℃冰箱保存 ,进行脑水肿定量、脑组织超氧化物歧化酶 (SOD)活性、丙二醛 (MDA)含量测定及脑组织伊文思兰含量测定。结果 与对照组相比 ,在缺血诱导时或再灌注开始时输注 2 5mg·kg-1PTX明显减轻沙鼠脑水肿的程度 (P <0 0 5或0 0 1) ,脑组织脂质过氧化产物MDA含量显著降低 (P <0 0 5或 0 0 1) ,脑组织中SOD的活性明显升高 (P <0 0 5或 0 0 1) ,脑组织伊文思兰含量显著降低 (P <0 0 5或 0 0 1)。 5 0mg·kg-1PTX输注对沙鼠脑缺血 /再灌注损伤无保护作用 ,其中 3只沙鼠死于低血压休克。结论 在血液动力学稳定的前提下 ,PTX对脑缺血 /再灌注损伤的保护作用可能与其提高脑血流量 ,抑制超氧阴离子产生 ,以及对血管内皮细胞的保护作用有关
Objective To observe the effect of pentoxifylline (PTX) on the global cerebral ischemia / reperfusion model in gerbils and to explore its mechanism. Methods The bilateral carotid arteries were occluded to induce global cerebral ischemia in gerbils. After 30 minutes, the brains were grafted and reperfused for 90 minutes. At ischemia induction, PTX at 25 mg · kg -1 or 50 mg · kg -1 was administered intravenously; another group received intravenous infusion of PTX at 25 mg · kg -1 at the beginning of reperfusion. Sham-operated group and control group received the same volume of 0.9% NaCl. At the beginning of reperfusion, all the gerbils were injected intraperitoneally with 0 2% Evans blue 1 ml · 10 0g-1. The brain was decapitated at the end of the experiment and stored in a refrigerator at 70 ℃. The brain edema was quantified, the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in brain tissue and the content of Evans blue in brain tissue were determined. Results Compared with the control group, infusion of 25 mg · kg-1 PTX at the induction of ischemia or at the beginning of reperfusion significantly reduced brain edema in gerbils (P <0.05 or 0.01) The MDA content of the oxidized product was significantly decreased (P <0.05 or 0.01), the activity of SOD in brain tissue was significantly increased (P <0.05 or 0.01), and the content of Evans blue in brain tissue was significantly decreased (P < 0 0 5 or 0 0 1). 5 0 mg · kg-1 PTX infusion had no protective effect on gerbil brain ischemia / reperfusion injury, of which 3 gerbils died of hypotension. Conclusions Under the condition of stable hemodynamics, the protective effect of PTX on cerebral ischemia / reperfusion injury may be related to the increase of cerebral blood flow, inhibition of superoxide anion generation and the protective effect on endothelial cells