白花丹参对促脑缺血再灌注后神经元再生的影响

摘要：目的：通过白花丹参干预大鼠局灶性脑缺血再灌注动物模型，探讨白花丹参对脑缺血再灌注后脑细胞再生及再生神经细胞分化的影响及影响机制。方法：采用线栓法制备大鼠局灶性脑缺血再灌注模型，给予白花丹参干预，分别从脑血流量、脑细胞凋亡率、新生脑细胞数量及新生神经细胞的分化等指标，观察白花丹参的脑保护作用及保护机制。结果：白花丹参具有增加脑血流量、降低脑细胞凋亡率、促进脑细胞再生及再生神经细胞的分化的作用。结论：缺血性脑损伤时白花丹参能显著的再加脑血流量、降低脑细胞凋亡率、促进脑细胞再生及再生神经细胞的分化。

Effects of Salvia miltiorrhiza Bge.f.alba on neuronal regeneration following cerebral ischemia/reperfusion**

BACKGROUND: Subsequent to cerebral ischemic injury, endogenous neural stem cells are activated, but ischemia-induced neuronal loss is not compensated by ischemic injury-induced neural regeneration. Salvia (S.) miltiorrhiza Bge.f.alba (Baihua Danshen, a Chinese herbal medicine) could enhance learning and memory functions, as well as promote neural regeneration. OBJECTIVE: To observe the effects of S. miltiorrhiza Bge.f.alba on recovery from cerebral ischemia-reperfusion injury, and the influence on neuronal regeneration and differentiation. DESIGN, TIME AND SETTING: Randomized, controlled, animal experiments were performed at the Experimental Animal Center and Neurobiology Laboratory of Taishan Medical College in September of 2006. MATERIALS: S. miltiorrhiza Bge.f.alba was provided by Taishan Medical College Botanic Garden, Taian, China; dl-3n-butylphthalide (NBP) soft capsule was purchased from NBP Pharmaceutical, Shijiazhuang, China; mouse anti-bromodeoxyuridine antibody, rabbit anti-NF200 antibody, and bromodeoxyuridine were purchased from Sigma, Louis, MO, USA; Annexin V-fluorescein isothiocyanate/PI apoptosis kit was purchased from Nanjing Comissariado Biological Technology Development, Nanjing, China. METHODS: Adult Sprague Dawley rats were randomly assigned to sham surgery, model (cerebral ischemia and reperfusion, without administration), S. miltiorrhiza Bge.f.alba, and NBP groups. Following establishment of the cerebral ischemia/reperfusion model, S. miltiorrhiza Bge.f.alba or NBP (1 mL/100 g) was respectively perfused at 30 minutes following cerebral ischemia/reperfusion. MAIN OUTCOME MEASURES: Alterations in cerebral blood flow before and after ischemia/reperfusion, NF200- and bromodeoxyuridine-double positive cells in striatum of affected tissues, as well as neuronal apoptosis rate at days 5 and 7 following cerebral ischemia/reperfusion.RESULTS: Subsequent to cerebral ischemia reperfusion, cerebral blood flow was reduced. Following treatment with S. miltiorrhiza Bge.f.alba, cerebral blood flow significantly increased (P < 0.05). NBP treatment was inferior to S. miltiorrhiza Bge.f.alba with regard to stabilization of cerebral blood flow (P < 0.05). S. miltiorrhiza Bge.f.alba significantly increased the number of newly formed neurons in rats following cerebral ischemia (P < 0.05) and significantly reduced neuronal apoptosis (P < 0.05), with no significant difference compared with NBP treatment (P > 0.05).CONCLUSION: S. miltiorrhiza Bge.f.alba significantly increased cerebral blood flow, reduced neuronal apoptosis, and promoted neuronal regeneration in rats with cerebral ischemia/reperfusion impairment. Key Words: cerebral ischemia/reperfusion; Salvia miltiorrhiza Bge.f.alba; apoptosis; neural stem cells; brain injury; neural regeneration