摘要
目的观察通心络胶囊对大脑中动脉闭塞(MCAO)模型大鼠脑缺血后微血管的保护作用。方法清洁级雄性 SD 大鼠200只随机分为5组:假手术组只做颈总和颈内动脉分离和生理盐水灌胃;其余4组制备 MCAO 模型,其中 MK-801组在造模成功后腹腔注射 MK-80I;通心络大、小剂量组均在造模成功后分别给予1.0 g·kg^(-1)·d^(-1)和0.5 g·kg^(-1)·d^(-1)通心络原粉水溶液灌胃;模型组给予等体积生理盐水灌胃。各组动物分别于术后6、12、24、48和72 h 电镜观察皮质微血管超微结构改变、检测缺血脑皮质毛细血管通透性、免疫组化法测定大脑皮质Ⅷ因子和脑微血管周围 IL-6、IL-1β蛋白表达。结果电镜下观察,治疗组均能显著改善缺血后脑皮质微血管超微结构;模型组脑内伊文蓝含量明显增加(P<0.01),通心络大剂量组在脑缺血12 h 能显著降低其含量(P<0.01),并且在24 h 后较小剂量组、MK-801组降低明显(P<0.01);模型组皮质中微血管数急剧减少(P<0.01),治疗组各时间皮质中血管数均明显多于模型组(P<0.01),其中通心络大剂量组的微血管数多于其他治疗组(P<0.01,P<0.05);模型组脑皮质微血管周围 IL-6及 IL-1β表达升高(P<0.01),分别于缺血后24和12 h 达到高峰,各治疗组与模型组相比,IL-6表达明显升高(P<0.01),而 IL-1β表达明显降低(P<0.01),其中通心络大剂量组最为明显(P<0.01)。结论通心络胶囊可从多角度对大脑中动脉闭塞(MCAO)模型大鼠脑缺血微血管损伤进行保护。
Objective To observe the protective effect of Tongxinluo on cerebral microvascular damage in rats with middle cerebral artery occlusion （MCAO） and provide an experimental foundation for the treatment of ischemia cerebrovascular disease from the view of microvascular protection. Methods 200 clean male SD rats were divided into five groups randomly： the sham group, the model group, high- and low-dose group of Tongxinluo capsule, MK-801 group. The number was same in every group. The sham group received separation of common carotid artery and internal carotid artery, while others underwent MACO. The rats of MK-801 group were injected with MK-801 into abdomen （0. 5 mg· kg^-1 · d^-1） after the model establishment. The rats of large dose Tongxinluo large group （ 1.0 g· kg^-1· d^-1 ） and small-dose group （0. 5 g · kg^-1·d^-1 ） were given suspension of fine powder respectively. The sham group and model group were given equal volume of normal saline. At the point of time in 6 h, 12 h, 24 h, 48 h and 72 h after surgery, electron microscope was used to observe cortex capillary after focal cerebral ischemia, Evans blue staining was adopted to determine microvascular permeability. The immunohistochemieal staining was used to detect the protein expression of Ⅷ factor, IL-6, IL-1β around the pallium microvessel. Results The ultrastructure in cerebral capillary was ameliorated effectively in all the therapeutic groups. The cerebral content of Evans blue in the model rats was higher than that of sham group （ P 〈 0. 01 ）. The Tongxinluo capsule significantly decreased the contents after 12 hours with a statistic difference from the small-dose group and the MK-801 group after 24 hours （ P 〈 0. 01 ）. The amounts of factor Ⅷ was less in cerebral microvasculariture of model rats than in other groups in every time point （ P 〈 0. 01, P 〈 0. 05 ）. Compared with sham group, the expression of IL-6 in cortex of model group increased significantly after ischemia（ P 〈 0. 01 ） and reached the peak in 24 hours（P 〈0. 01 ）, however still lower than that of the therapeutic groups （P 〈0. 01）. Compared with sham group, the expression of IL-1β in cortex of the model group increased significantly after ischemia （ P 〈 0. 01 ） and reached the highest within 12 hours （ P 〈 0. 01 ）, however decreased significantly in the therapeutic groups, especially in Tongxinluo large-dose group （ P 〈 0. 01 ）. Conclusion The Tongxinluo capsule protects the damaged cerebral microvessels of the MCAO rats on different aspects.
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2007年第1期54-58,共5页
Chinese Journal of Neurology
关键词
心血管药物(中药)
动脉闭塞性疾病
脑缺血
Cardiovascular agents （TCD）
Arterial occlusive diseases
Brain ischemia
