丁苯酞对大鼠局灶性脑缺血再灌注损伤的保护作用

目的 观察丁苯酞对大鼠局灶性脑缺血再灌注损伤后血管内皮生长因子(VEGF)表达的影响及其对缺血再灌注损伤治疗时间窗的影响.方法 SD大鼠72只,随机分为假手术组24只,缺血再灌注组24只,丁苯酞治疗组24只.每组再分为缺血2、3和4 h 后再灌注3个亚组,每亚组8只.采用改良线栓法制作大鼠局灶性脑缺血再灌注模型,观察各组神经功能和脑梗死范围,免疫组化法检测脑组织中VEGF表达.结果 随着缺血时间延长,再灌注后,神经功能评分和脑梗死范围也随之增高,缺血再灌注组在缺血2、3和4 h的神经功能评分分别为(2.6 ± 0.6)分、(3.7 ± 1.0)分和(4.2 ± 1.0)分,脑梗死容积比率分别为(27.6 ± 5.4)%、(33.1 ± 6.1)%和(42.3 ± 7.3)%;而在丁苯酞治疗组则分别为(1.2 ± 0.5)分、(1.6 ± 0.7)分、(2.3 ± 0.9)分和(9.8 ± 1.6)%、(16.7 ± 2.3)%和(20.7 ± 3.9)%,与缺血再灌注组比较丁苯酞治疗组明显较低,差异有统计学意义(P值均＜ 0.05).并发现丁苯酞治疗组的缺血4 h的症状评分和脑梗死容积比率与缺血再灌注组缺血2 h比较,差异无统计学意义(P ＞ 0.05).随着缺血时间的延长,丁苯酞治疗组和缺血再灌注组的VEGF表达均逐渐减弱.与假手术组比较,缺血再灌注组脑组织中VEGF表达明显减弱(P ＜ 0.01).与其他两组比较,丁苯酞治疗组的VEGF表达明显较强,差异有统计学意义(P ＜ 0.01).结论 丁苯酞对大鼠局灶性脑缺血再灌注损伤具有保护作用,其作用机制可能与VEGF表达相关,并能延长缺血再灌注治疗时间窗.

The protective effect of dl-3n-butylphthalide on local cerebral ischemia-reperfusion injury in experimental rats

Objective To observe the effect of dl-3n-butylphthalide(NBP) on the expression of vascular endothelial growth factor(VEGF) in the rat model with focal cerebral ischemia-reperfusion injury and to discuss its impart on the therapeutic time window for cerebral ischemia-reperfusion injury.Methods Seventy-two SD rats were randomly and equally divided into three groups with 24 rats in each group:sham operation(SO) group,ischemia-reperfusion(I-R) group and NBP group;and each group was again randomly and equally subdivided into three subgroups:2-hour,3-hour and 4-hour reperfusion subgroup according to the reperfusion time after ischemia.By using modified suture embolus method the focal cerebral ischemia-reperfusion model was established.The experimental models were kept under close observation for the extent of cerebral infarction and the neurological deficit.The expressions of VEGF in the brain tissues were determined with immunohistochemical method.The results were statistically analyzed and compared among different groups.Results As the ischemia time went on,the extent of cerebral infarction and the neurological deficit after reperfusion increased.The severity of cerebral infarction and the neurological deficit in NBP group was significantly lower than that in I-R group,the difference between the two groups was significant(P<0.05).The extent of cerebral infarction and the neurological deficit of ischemia observed in the 4-hour subgroup of NBP group was quite similar to that observed in the 2-hour subgroup of I-R group,the difference was not significant(P>0.05).Along with the increased ischemia time the expressions of VEGF in brain tissues in both NBP group and I-R group were significantly decreased(P<0.01).The expression level of VEGF in NBP group was significantly higher than those in both I-R group and SO group(P<0.01).Conclusion The dl-3n-butylphthalide has a protective effect on focal cerebral ischemia-reperfusion injury.Its mechanism may be associated with VEGF expression level.The use of dl-3n-butylphthalide can prolong the therapeutic time window of reperfusion.