依达拉奉对蛛网膜下腔出血后大鼠早期脑损伤的神经保护作用。

Neuroprotective effects of edaravone on early brain injury in rats after subarachnoid hemorrhage.

机构信息

Department of Neurology, First Affiliated Hospital of Nanjing Medical University, Jiangsu, China.

出版信息

Chin Med J (Engl). 2009 Aug 20;122(16):1935-40.

PMID:19781374

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.

摘要

背景

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。

方法

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。

结果

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）。