丁苯酞对实验性动脉血栓形成性脑梗死的治疗作用

Effects of dl-3n-butyphthalide in the treatment of rat cerebral infarction with middle cerebral artery occlusion

目的:观察丁苯酞(恩必普)对实验性动脉血栓形成性脑梗死的治疗作用.方法:按已定型的双肾双夹法建立易卒中型肾血管性高血压大鼠(RHRSP)模型,用光化学法造成大脑中动脉闭塞(MCAO)致大脑中动脉血栓形成.94只MCAO大鼠随机分为丁苯酞治疗组、生理氯化钠溶液(NS)对照组各47只,另取3只RHRSP作为假手术组.治疗组于MCA闭塞d1起po丁苯酞150 mg·kg-1,bid,给药10 d.每日行神经行为学评分, d10处死大鼠取脑进行TTC染色及常规病理检查,观察局部血栓梗死灶微血管等的变化.结果:丁苯酞治疗1～6d的神经行为学评分均明显增加(如d4治疗组(17.14±0.38)分, NS组(15.29±1.11)分,P<0.05);治疗组梗死面积为(6.94±2.11)mm2,梗死灶占前脑面积百分比在治疗组为(1.82±0.50)%,均显著低于NS组[(8.90±1.96)mm2和 (2.40±0.65)%,均为P<0.05];治疗组局部血栓变小、梗死灶及周围微血管增生也显著多于NS组(79% vs 62%,P<0.05),灶内出血发生率减少.结论:丁苯酞可改善病灶局部循环,减小梗死面积,减轻脑组织损伤,恢复神经功能.

Objective：To study the effects of dl-3n-butyphthalide （NBP） in the treatment of cerebral infarction with middle cerebral artery occlusion （MCAO） in rats. Methods： After the renal arteries were constricted bilaterally with ring-shape silver clips, the stroke-prone renovascular hypertensive rats（RHRSP） were established. Subsequently, 94 RHRSP were resulted in MCAO by a photochemical reaction. These rats with the MCAO were randomized 1 ： 1 to be treated with NBP （ 150 mg·kg^-1 , bid） or normal saline in 24 hours after the MCAO for 10 days. Additional 3 RHRSP were used as a sham group. Daily neurobehaviors of these rats were scored in the 10-day course of the treatment by a Garcia test. Following after the euthanasia of the rats at the end of the treatment, the cerebral tissues were removed and then stained with triphenyhle trazolium chloride （TTC）. The histopathological examinations on the occlusive site and size of local microvascular and cerebral hemorrhagic lesions were conducted by operation microscope and microphotography. Results：The NBP rats had significantly higher Garcia scores than the saline rats （ P 〈 0.05 ）. The NBP rats significantly experienced a less infarct area and a smaller ratio of infarct area over antecerebral compared with the saline rats, （6.94 ± 2.11 ） mm^2 vs. （ 8.90 ±1.96） mm^2 and （ 1.82 ± 0.50） % vs. （2.40 ± 0.65） %, respectively （P 〈 0.05）. The occlusive size and incidence of cerebral hemorrhage in the NBP rats were significantly reduced compared with the one in the saline rats. The microvessels at the occlusive site were much more enriched in the NBP rats than in the saline rats （79% vs. 62%, P 〈 0.05）. Conclusion： NBP might correct the dysfunctional neurobehaviors by improving the circulation of the occlusive lesions and inhibiting further formation of cerebral infarction.