Department of Neurology, First Affiliated Hospital of Nanjing Medical University, Jiangsu, China.
Chin Med J (Engl). 2009 Aug 20;122(16):1935-40.
The underlying mechanism of early neurobiological impairment after subarachnoid hemorrhage (SAH) is not well understood, but the system of reactive oxygen superoxide (ROS) might be involved. Edaravone (MCI-186), a potent free radical scavenger that prevents apoptosis of neurons, was thus used in this study to see its possible therapeutic effect in early brain injury due to SAH in a rat model.
One hundred and twenty male Sprague-Dawley rats were randomly assigned to four groups: group 1, control rats receiving sham operation only; group 2, rats with SAH treated by saline; group 3, rats with SAH treated with 1 mg/kg MCI-186 injected intraperitoneally; and group 4, rats with SAH treated with 3 mg/kg MCI-186. Treated with either saline or MCI-186 twice daily for two consecutive days after SAH, the rats were sacrificed for measurements of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) and histological analysis of caspase-3 protein by Western blotting and immunohistochemical staining. In addition, mortality and neurological scores were statistically analyzed by the chi-square test and Dunn's procedure respectively for each group. One-way analysis of variance followed by the Tukey's procedure was also used in data analysis.
The rats in group 2 that received saline only showed neurological impairment as well as elevated mortality, and were found to have significantly increased levels of MDA and caspase-3, but reduced SOD activities in brain tissues (P < 0.05). When treated with MCI-186 at two different dosages, the rats in groups 3 and 4 had markedly decreased levels of MDA and caspase-3 but increased SOD activities in the brain tissue (P < 0.05), along with improved scores of neurological evaluation (P < 0.05).
This study sheds some lights on the therapy of SAH-induced early brain injury by providing the promising data indicating that MCI-186, a radical scavenger, can efficiently diminish apoptosis of neurons and thus prevent the function loss of the brain in rats with SAH.
蛛网膜下腔出血（SAH）后早期神经生物学损伤的潜在机制尚不清楚，但活性氧超氧化物（ROS）系统可能参与其中。依达拉奉（MCI-186）是一种有效的自由基清除剂，可防止神经元凋亡，因此本研究旨在观察其在 SAH 大鼠模型早期脑损伤中的可能治疗作用。
120 只雄性 Sprague-Dawley 大鼠随机分为 4 组：1 组，仅接受假手术的对照大鼠；2 组，SAH 大鼠用生理盐水治疗；3 组，SAH 大鼠用 1mg/kg MCI-186 腹腔注射治疗；4 组，SAH 大鼠用 3mg/kg MCI-186 治疗。在 SAH 后连续两天每天两次用生理盐水或 MCI-186 治疗，然后处死大鼠，测量丙二醛（MDA）和超氧化物歧化酶（SOD）的活性，并通过 Western 印迹和免疫组织化学染色分析半胱氨酸天冬氨酸蛋白酶-3（caspase-3）蛋白。此外，通过卡方检验和 Dunn 程序分别对每组的死亡率和神经评分进行统计学分析。采用单因素方差分析，随后采用 Tukey 程序进行数据分析。
仅接受生理盐水治疗的 2 组大鼠表现出神经功能障碍和死亡率升高，并且发现脑组织中 MDA 和 caspase-3 水平显著升高，而 SOD 活性降低（P<0.05）。用两种不同剂量的 MCI-186 治疗时，3 组和 4 组大鼠脑组织中 MDA 和 caspase-3 水平明显降低，SOD 活性升高（P<0.05），神经功能评估评分改善（P<0.05）。
本研究通过提供有希望的数据，为 SAH 诱导的早期脑损伤治疗提供了一些启示，表明自由基清除剂依达拉奉可有效减少神经元凋亡，从而防止 SAH 大鼠的脑功能丧失。
