摘要： 目的   观察6%羟乙基淀粉130/0.4 对全脑缺血-再灌注损伤大鼠血-脑屏障通透性的影响，并探讨其可能的作用机制。方法   采用三血管阻断法建立大鼠全脑缺血-再灌注损伤模型，分别于全脑缺血前10 min、脑缺血10 min、再灌注后10 min 采集股动脉血检测动脉血氧分压和二氧化碳分压；干湿重法计算脑组织含水量，伊文蓝渗出量评价血-脑屏障通透性，免疫组织化学染色和酶联免疫吸附试验检测核因子-κBp65 活性和脑组织匀浆肿瘤坏死因子-α质量浓度。结果   手术前后不同观察时间点、不同处理组之间比较，动脉血氧分压和二氧化碳分压差异均无统计学意义（P > 0.05）。单纯缺血组、生理盐水组和羟乙基淀粉组大鼠脑组织核因子-κBp65 表达水平升高，免疫组织化学评分（IHS）增加（均P =0.000），其中羟乙基淀粉组大鼠两项指标显著低于其他两组（均P = 0.000）。缺血-再灌注损伤后，单纯缺血组和生理盐水组大鼠脑组织含水量和血-脑屏障通透性显著高于羟乙基淀粉组（均P = 0.000），而羟乙基淀粉组此两项检测指标均接近正常值范围（P > 0.05）。结论   6%羟乙基淀粉130/0.4 能够改善大鼠全脑缺血-再灌注损伤时的血-脑屏障功能，降低其通透性，减轻脑水肿，具有一定的脑保护作用；其作用机制与抑制肿瘤坏死因子-α和核因子-κBp65表达、减轻炎性损伤有关。

关键词: 再灌注损伤, 血脑屏障, 羟乙基淀粉, 免疫组织化学, 酶联免疫吸附测定, 疾病模型, 动物

Abstract: Objective To observe the effect of hydroxyethyl starch (HES) 130/0.4 on global cerebral ischemia-reperfusion in rats, and to investigate the underlying mechanism of HES130/0.4. Methods Forty-eight Sprague-Dawley (SD) rats were divided randomly into 4 groups, namely sham operation group (S group), ischemia-reperfusion group (IR group), normal saline (NS) + IR group (NS group) and HES130/0.4 + IR group (HES group). The blood gas analysis was performed during the experiment. The content of tumor necrosis factor-α (TNF-α), evans blue (EB), brain water content and nuclear factor-κB (NF-κB) activity in brain tissue were determined at 12 h after the experiment. Results No significant differences of arterial partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2) in every group were seen at different observation time before and after operation (P > 0.05, for all). NF-κBp65 expression and Immunohistochemical Score (IHS) of brain tissue were all increased in IR group, NS group and HES group (P = 0.000, for all), while NF-κBp65 expression and IHS score in HES group were lower than those in other 2 groups (P = 0.000, for all). After ischemia-reperfusion injury, brain water content and blood-brain barrier (BBB) permeability in IR group and NS group were all significantly higher than those in HES group (P = 0.000, for all), while the 2 indices in HES group were all nearly approaching to normal range (P > 0.05, for all). Conclusion HES130/0.4 can alleviate ischemia-reperfusion BBB injury in ischemia-reperfusion rats. HES130/0.4 has cerebral protective effect, and the underlying mechanism may concerned with the decrease of TNF-α and NF-κB expression and attenuation of inflammatory injury.

Key words: Reperfusion injury, Blood-brain barrier, Hetastarch, Immunohistochemistry, Enzyme-linked immunosorbent assay, Disease models, animal