氧化应激在慢性缺血性脑白质损伤中的作用

Effects of oxidative stress on white matter damage in rats model of chronic cerebral hypoperfusion

目的阐明氧化应激是否参与大鼠慢性脑缺血所致的脑白质损伤。方法健康雄性Wistar大鼠按照完全随机数字表法分为假手术组，持久性双侧颈总动脉结扎3d组、7d组、3周组及6周组，每组6只。应用大鼠双侧颈总动脉结扎制备慢性脑缺血模型，检测大鼠脑白质内超氧化物歧化酶（SOD）活性、过氧化氢酶（CAT）活性、谷胱甘肽（GSH）含量以及脂质过氧化产物丙二醛（MDA）和4-羟基壬烯醛（4-HNE）加合物的变化。结果与假手术组比较，慢性脑缺血大鼠脑白质内MDA含量在手术后3周明显增加，手术后6周进一步增高，差异有统计学意义（P〈0．05）。手术后3d至6周，慢性脑缺血大鼠脑白质内4-HNE蛋白加合物逐渐增高，与假手术组比较有差异有统计学意义（艮0．05）。SOD活性在手术后3周和6周才明显降低，与假手术组比较差异有统计学意义（P〈0．05）。此外，慢性脑缺血大鼠脑白质内GSH含量在手术后7d即开始降低，而在手术后3周及6周则进一步下降，与假手术组比较差异有统计学意义（P〈0．05）。结论慢性脑缺血导致大鼠脑白质氧化性损伤增加，抗氧化防御能力降低；氧化性损伤的增加和抗氧化防御能力的降低与慢性脑缺血所致的脑白质损伤密切相关。

Objective To clarify the participation of oxidative stress in the white matter lesions induced by chronic cerebral hypoperfusion in the rats. Methods Chronic cerebral ischemia models were established by permanent occlusion of bilateral common carotid arteries （2-VO） in male Wistar rats. The rats were assigned to 5 groups （n=6）： those with chronic cerebral ischemia for 3 and 7 d, 3 and 6 weeks, and those given sham operation. We examined the activities of superoxide dismutase （SOD） and catalase （CAT）, the glutathione （GSH） content and the changes of malondialdehyde （MDA） level and HNE modified protein in the white matter of rats. Results The MDA level of the hypoperfused rats was significantly increased 3 weeks after the operation as compared with that of the sham-operated rats with a further increase at 6 weeks （P〈0.05）. The HNE modified protein level in the hypoperfused rats was gradually and significantly increased from 3 d to 6 weeks after the operation as compared with that of the sham-operated rats （P〈0.05）. SOD activity of the hypoperfused rats was significantly decreased 3 and 6 weeks after the operation compared with that of the sham-operated rats （P〈0.05）, while CAT activeity was not altered. Moreover, the GSH content in the hypoperfused rats was gradually and significantly decreased 7 d and 6 weeks after the operation in comparison with that in the sham-operated rats （P〈0.05）. Conclusion Chronic cerebral ischemia results in increased oxidative damage in the white matter and decreased antioxidant defense capability, which is closely correlative to white matter lesions induced by chronic cerebral ischemia.