Cole D J, Nary J C, Drummond J C, Patel P M, Jacobsen W K
Department of Anesthesiology School of Medicine Loma Linda University, California 92354, USA.
Artif Cells Blood Substit Immobil Biotechnol. 1997 Jan-Mar;25(1-2):141-52. doi: 10.3109/10731199709118906.
Prior studies indicate that alpha-alpha diaspirin crosslinked hemoglobin (DCLHb) decreases cerebral ischemia. One mechanism whereby DCLHb may ameliorate cerebral ischemia is by binding nitric oxide (NO), which has been implicated as neurotoxic. We assessed the effect of L-NAME (NO synthase inhibitor) and L-arginine (NO substrate) on ischemic brain injury after DCLHb infusion. Rats were randomized to one of the following groups: Control-no hematocrit manipulation; DCLHb-hematocrit decreased to 16% with 10% DCLHb; DCLHb/L-NAME-hematocrit decreased to 16% with DCLHb, and L-NAME given; DCLHb/L-arg-hematocrit decreased to 16% with DCLHb, and L-arginine given. After 90-min of middle cerebral artery occlusion and 4-hr of reperfusion, infarct volume was determined with TTC stain. Infarct volume (mm3, mean +/- SD) was greater in the Control group (142 +/- 16) than the DCLHb (43 +/- 12), DCLHb/L-NAME (45 +/- 14), and DCLHb/L-arg (71 +/- 18) groups (p < 0.05); was greater in the DCLHb/L-arg group than the DCLHb and DCLHb/L-NAME groups (p < 0.05); but was not different between the DCLHb and DCLHb/L-NAME groups. These data indicate that DCLHb decreases ischemic brain injury, and that binding NO may be one mechanism by which DCLHb decreases ischemic brain injury.
先前的研究表明，α-α双阿司匹林交联血红蛋白（DCLHb）可减轻脑缺血。DCLHb改善脑缺血的一种机制可能是通过结合一氧化氮（NO），而一氧化氮已被认为具有神经毒性。我们评估了L-NAME（一氧化氮合酶抑制剂）和L-精氨酸（一氧化氮底物）对输注DCLHb后缺血性脑损伤的影响。将大鼠随机分为以下几组：对照组——不进行血细胞比容处理；DCLHb组——血细胞比容降至16%，同时输注10% DCLHb；DCLHb/L-NAME组——血细胞比容降至16%，输注DCLHb并给予L-NAME；DCLHb/L-arg组——血细胞比容降至16%，输注DCLHb并给予L-精氨酸。大脑中动脉闭塞90分钟并再灌注4小时后，用TTC染色法测定梗死体积。梗死体积（mm³，均值±标准差）在对照组（142±16）大于DCLHb组（43±12）、DCLHb/L-NAME组（45±14）和DCLHb/L-arg组（71±18）（p<0.05）；在DCLHb/L-arg组大于DCLHb组和DCLHb/L-NAME组（p<0.05）；但DCLHb组和DCLHb/L-NAME组之间无差异。这些数据表明，DCLHb可减轻缺血性脑损伤，且结合NO可能是DCLHb减轻缺血性脑损伤的机制之一。
