一氧化碳对脑缺血脂质过氧化物及Na^＋-K^＋ATP酶的影响及其限速酶在脑缺血中的表达

Effect of carbon monoxide on lipid peroxidation and activities of Na^＋ -K^＋ ATPase in focal ischemic brain tissue and the neuronal expression of heme oxygenase protein in rats

目的观察一氧化碳（CO）对局灶性脑缺血脑组织脂质过氧化物及Na^＋K^＋ATP酶的影响以及血红素氧合酶（HO-1）在脑缺血中的表达。方法将sD大鼠随机分为3组，使用HO诱导剂、HO抑制剂腹腔注射为实验组，对照组注人生理盐水，12h后制备大鼠局灶性脑缺血模型。缺血后24h检测CO浓度、丙二醛（MDA）、超氧化物歧化酶（SOD）及Na^＋-K^＋ATP酶活性。对大鼠脑缺血后早期不同时间点进行HO-1免疫组织化学及病理学研究，并应用计算机图像分析技术检测HO-1表达的强弱。结果与对照组比较，HO诱导剂组CO浓度显著升高1．36倍（P〈0．01），HO抑制剂组CO浓度显著降低26．4％（P〈0．01）。HO诱导剂组MDA减少11．3％（P〈0．01），SOD及Na^＋-K^＋ATP酶活性分别升高6．8％和20．1％（P均〈0．05），而HO抑制剂组MDA增加12．4％（P〈0．05），SOD及Na^＋-K^＋ATP酶活性分别降低8．2％和18．9％（P均〈0．05）。免疫组织化学显示缺血后30min神经元和胶质细胞即有HO-1阳性表达，随着时间推移，HO-1的表达逐渐增强。结论CO可对局灶性缺血的脑组织起保护作用。脑缺血时脑内HO-1的表达可能是脑组织对自身损伤的恢复机制之一。

Objective To study the effect of carbon monoxide （CO） on lipid peroxidation and activities of Na ^＋ -K^ ＋ ATPase of local cerebral ischemia and the expression of heme oxygenase protein during early focal ischemia in rats. Methods SD rats were divided into three groups randomly,including hemin group,ZnPP group and saline group. Twelve h before, and 24 h after infarction, the concentrations of CO and MDA, and activities of SOD and Na ^＋ -K^ ＋ ATPase were examined. The expression of heme oxygenase-1 （ HO-1 ） protein in the brain of rats during early focal cerebral ischemia was detected by using immunohistochemistry and computer image analysis in middle cerebral artery occlusion （MCAO） model of rats. Results Compared with the saline group, the concentration of CO in blood was significantly increased by 1.36-fold in Hemin group （P 〈 0.01 ）, and that was significantly decreased by 26.4% in ZnPP group （P 〈0.01 ）. In Hemin group,MDA was decreased by 11.3% （P 〈0.01 ） and the activities of SOD and Na^＋ -K ^＋ ATPase were increased by 6.85% and 20.1% respectively （ all P 〈 0.05 ） as compared with saline group. In ZnPP group, MDA was increased by 12.4% （P 〈 0.05 ）, but the activities of SOD and Na^＋ -K^ ＋ ATPase were decreased by 8.2% and 18.9% respectively （ all P 〈 0.05 ） in comparison to saline group. HO-1 expression was detectable in the neurons and gliacytes of the ipsilateral cerebral cortex infarction area at 30 rain after MCAO. With time going on, the expression of HO-1 was increased. Conclusion CO can protect brain tissues with focal cerebral ischemia. The expression of HO-1 protein is evidently significant physiological consequences in the recovery of neuronal tissue from ischemic injury in focal cerebral ischemia.