异丙酚对缺血再灌注损伤大鼠海马线粒体能量代谢、ATP酶活性及自由基系统的影响

目的: 观察异丙酚对缺血再灌注损伤大鼠海马线粒体能量代谢、ATP酶活性、脂质过氧化及超微结构的影响。方法: 雄性Wistar 大鼠30 只,随机分为假手术组、缺血再灌注对照组和缺血再灌注异丙酚处理组。采用大鼠全脑缺血再灌注损伤模型。全脑缺血10 min 再灌注60 min 时,断头处死大鼠。检测海马线粒体三磷酸腺苷(ATP)、丙二醛(MDA)含量及Na⁺-K⁺-ATP酶、Ca²⁺-ATP酶、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)活性并观察线粒体超微结构的改变。结果: 缺血再灌注后海马线粒体的ATP含量及Na⁺-K⁺-ATP酶、Ca2+-ATP酶、SOD、GSH 活性均有不同程度的降低,MDA 含量增高,线粒体超微结构亦发生明显损害;麻醉相关剂量的异丙酚可使ATP含量、Na⁺-K⁺-ATP酶、Ca²⁺-ATP酶、SOD、GSH活性有不同程度的恢复,并降低MDA 的含量,减轻线粒体损伤的程度。结论: 异丙酚对脑缺血再灌注损伤的保护作用可能与其抑制线粒体脂质过氧化反应,清除自由基,保持线粒体结构的完整性,促进线粒体ATP含量和ATP酶活性的恢复有关。

Effects of propofol on ATP content,ATPase activity and lipid peroxidation of hippocampus mitochondrial following global ischemia-reperfusion in rats

AIM: To investigate the effects of propofol on the ATP content, ATPase activity, lipid peroxidation and ultrastructure in hippocampus mitochondrial in rats following global ischemia-reperfusion.METHODS: Global ischemia-reperfusion was induced by the use of 4-vessel occlusion method in a rat model.30 male Wistar rats were randomly divided into three groups:sham operation group (n=10), ischemia-reperfusion control group(n=10), and propofol treated group, 100 mg·kg^-1 propofol before ischemia (n=10).After global ischemia 10 min and reperfusion 60 min, rats were decapitated and the brains removed.The contents of ATP and MDA, activities of Na⁺-K⁺-ATPase, Ca²⁺-ATPase, SOD and GSH in hippocampus mitochondrial were measured, and mitochondrial structure was observed by electron microscope.RESULTS: The content of ATP, activities of Na⁺-K⁺-ATPase, Ca²⁺-ATPase, SOD and GSH decreased significantly, and the content of MDA increased obviously in the hippocampal mitochondrial after ischemia-reperfusion. Propofol significantly improved the decrement levels of ATP, Na⁺-K⁺-ATPase, Ca²⁺-ATPase, SOD and GSH, and inhibited the content of MDA increased in hippocampal mitochondrial.Electron microscopic examination also showed that mitochondrial damage was milder in propofol treated group than that in ischemia-reperfusion control group. CONCLUSION: Neuroprotective effects of propofol may be related to the inhibited mitochondrial lipid peroxidation, the integrality protected in mitochondrial structure, and the improved mitochondrial energy metabolism and ATPase activity after global ischemia-reperfusion.