参芎滴丸对大鼠脑缺血再灌注后神经可塑性的影响

Influence of Shenxiong Dripping Pill on neural plasticity after cerebral ischemia and reperfusion in rats

目的观察参芎滴丸(黄芪、丹参、川芎等的提取物组成)对大脑中动脉闭塞大鼠模型缺血脑组织神经生长相关蛋白43(Growth associated protein-43,GAP-43)、突触素(Synaptophysin,SYN)表达的影响及5-溴脱氧尿嘧啶核苷(Bromode-oxyuridine,BrdU)的标记反应,探讨其促进脑缺血后神经可塑性的机制。方法用线栓法阻断大脑中动脉,建立大鼠局灶性脑缺血再灌注损伤模型,用HE染色及免疫组化方法观察缺血脑组织的病理学变化及GAP-43、SYN的表达及BrdU标记反应情况。结果细胞坏死模型组最为明显,并可见核固缩、碎裂,用药组细胞坏死较模型组轻,假手术组和空白组胞核完整,核仁清晰,胞质淡染,细胞与间质分界清楚。在大鼠缺血损伤后第7天,模型组脑内GAP-43和SYN的表达显著增加,相比模型组,用药组脑内损伤区周围GAP-43及SYN显著增加;模型组脑内损伤区对BrdU的摄取显著增加,与模型组相比,用药组脑内损伤区周围BrdU标记反应显著增加。结论参芎滴丸能够上调脑损伤修复过程中神经元突起生长相关蛋白的表达及内源性神经干细胞的增殖与分化,从而促进缺血损伤后的神经可塑性。

AIM To explore the influence of Shenxiong Dripping Pill（the extractions of Astragali Radix,Salviae miltiorrhizae Radix et Rhizoma,Chuanxiong Rhizoma and etc.） in the treatment for neural plasticity and to study its mechanism by observing the changes of growth-associated with protein-43（GAP-43）,synaptophysin（SYN） and labelled reaction of bromodeoxyuridine（BrdU） in the tissues of cerebral ischemia.METHODS Middle cerebral artery occlusion model was replicated by string ligation.HE and immunohistochemical staining methods were used to observe the brain ischemia pathological changes,expressions of GAP-43,SYN,and labelled reaction of BrdU in the tissues of cerebral ischemia.RESULTS Necrocytosis in string ligation group was most common with karyopyknosis and fragments.Necrocytosis in the treatment group was lower than that in the model group.Sham and blank group had clear nucleoli,light dyed cytoplasm and distinctive borders.On the 7th day after ischemic injury,there were significant expressions of GAP-43 and SYN in string ligation group.As compared with the model group,the expressions of GAP-43 and SYN showed significant growth in the injury area in the trcatment group.Intake of BrdU in injury area presented the same trend.CONCLUSION These results suggest that Shenxiong Dripping Pill can increase the expressions of neurites growth related to proteins and promote endogenous neural stem cells proliferation and differentiation,and consequently promote the the neural plasticity after ischemic injury.