大剂量岷当归配伍川芎对脑缺血再灌注损伤的神经保护作用

The Protective Effects of Combination of MinDangGui and ChuanXiong in Large Doses on the Nerve Dysfunction Induced by Cerebral Ischemia-Reperfusion Injury

目的:通过观察大剂量岷当归配伍川芎对大鼠脑缺血再灌注损伤后神经功能评分、脑梗死体积及脑组织中ICAM-l、COX-2基因表达的影响,研究不同剂量岷当归配伍川芎对大鼠脑缺血再灌注损伤的神经保护作用及机制。方法:将60只雄性Wistar大鼠60只,随机分为6组,即假手术组、模型组、尼莫地平组、岷当归高剂量+川芎组、岷当归中剂量+川芎组、岷当归低剂量+川芎组,每组各10只。模型采用大脑中动脉缺血模型。在造模前12小时、30分钟各给药1次,缺血后12、24、36、48小时各给药1次。缺血再灌注48小时将大鼠处死,留取标本。对各组大鼠进行行为学评估,采用TTC染色法检测各组大鼠脑梗死体积,免疫组化及RT-PCR检测ICAM-l、COX-2m RNA的相对表达。结果:神经功能评分、梗死面积比率岷当归+川芎治疗组与尼莫地平组均低于模型组,差异有统计学意义(P<0.05)。ICAM、COX-2m RNA表达模型组与假手术组比较,差异有统计学意义(P<0.05),各治疗组与模型组比较,差异有统计学意义(P<0.05);岷当归高剂量+川芎组与岷当归中剂量+川芎组比较,差异无统计学意义(P>0.05)。结论:高、中剂量组岷当归与川芎配伍可以抑制脑缺血再灌注损伤过程的炎症反应,改善神经缺损症状,在一定程度上缩小缺血再灌注损伤后大鼠脑组织梗死体积,降低炎症因子在脑缺血再灌注损伤中的表达,从而减轻脑细胞的损伤。

Objective： To study the protective effects and mechanisms of MinDangGui （Angelica sinensis） combined with ChuanXiong （Ligusticum wallichii） in different doses on the rats with cerebral ischemia reperfusion injury （CIRI） by observing the effects of MinDangGui and ChuanXiong in large doses on neural function scores, cerebral infarction size and ICAM-1 and COX-2 gene expressions of the rat model. Methods： Sixty male Wistar rats were divided into six groups, the sham operation group, the model group, the nimodipine group, the high, moderate and low dosages groups of MinDangGui and ChuanXiong, ten rats each group. The model was prepared by middle cerebral artery occlusion. The rats were given drugs once separately about 12 hours and30 minutes before modeling, in 12, 24, 36 and 48 hours after ischemia. They were sacrificed in 48 hours after ischemia reperfusion and the samples were kept. Behavioral assessment was performed for each group, cerebral infarction size of the rats in different groups was detected by TTC staining method, and meanwhile relative expressions of ICAM-1 and COX-2mRNA were measured by immunohistochemical method and RT-PCR. Results： The treatment group of MinDangGui and ChuanXiong was lower than the model group in neural function scores, cerebral infarction size rate, there were statistical differences （P〈0.05）. When the model group was compared with the sham operation group in ICAM and COX-2mRNA expressions, there were statistical differences （P〈0.05）, when all the treatment groups were compared with the model group, there were statistical differences （P〈0.05）; when the high dosage group of MinDangGui and ChuanXiong was compared with the middle dosage group of MinDangGui and ChuanXiong, there was no statistical differences（P〉0.05）. Conclusion： The high, middle dosages of MinDangGui and ChuanXiong can inhibit inflammatory reaction in the course of cerebral ischemia-reperfusion injury, improve neural defective symp- toms, and reduce cerebral infarction size of the rats after ischemia-reperfusion injury to a certain degree, as well as lower inflammatory factor expression in cerebral ischemia-reperfusion injury, therefore it can alleviate the injury of cerebral cells.