Objective To investigate the effect of Shenxiong Huayu Capsules on the expression of Notch1/GAP-43 after global cerebral ischemia reperfusion in hippocampus. Methods One hundred healthy male SD rats were randomly di-vided into 4 groups:sham operation group (n=25), cerebral ischemia reperfusion group (n=25) and Shenxiong Huayu Capsules low-dose group (n = 25) and high-dose group (n = 25). The gavage dose of Shenxiong Huayu Capsules low-dose group and high-dose group was 240, 480 mg/(kg·d), the sham operation group and cerebral ischemia reperfusion group were given distilled water according to 10 mL/kg weight, once every 8:00 am, for 7 days. The model of global cerebral ischemia reperfusion was made by improved four-vessel occlusion according to Pulsinelli 4 vascular occlusion (4-VO) method, and the rats were sacrificed at 1, 2, 3, 7 d and 14 d respectively after injury to take the hippocampus tissues. HE staining was used to detect morphological changes in hippocampus each point in time; and the expressions of Notch1 (1, 2, 3 d) and GAP-43 (3, 7, 14 d) were measured by immunohistochemistry. The sensorimotor functions of the rats were detected by beam walking test on 1-3 days after injury. Results Compared with sham operation group, the neuron counts of rats in cerebral ischemia reperfusion group was significantly decreased (P<0.05). The expressions of Notch1 (1-3 days after injury) and GAP-43 (3, 7, 14 d after injury) in cerebral ischemia reperfusion group were en-hanced obviously at the corresponding time (P<0.05), and the scores of beam walking test were decreased obviously in cerebral ischemia reperfusion group (P<0.05). Compared with cerebral ischemia reperfusion group, the neuron counts were decreased obviously in Shenxiong Huayu Capsule low-dose group (P<0.05), the expressions of Notch1 and GAP-43 were furthe r increased in Shenxiong Huayu Capsules low-dose group (P< 0.05), and the scores of beam walking test improved significantly in Shenxiong Huayu Capsules low-dose group (P<0.05). The above indexes mentioned changes were more noteworthy in Shenxiong Huayu Capsules high-dose group (P < 0.05). The expressions between Notch1 and GAP-43 had a positive correlation with each other in cerebral ischemia reperfusion group and Shenxiong Huayu Capsules low-dose group (r= 0.838, P< 0.01;r = 0.786, P< 0.01). Conclusion The neuroprotective effect of Shenxiong Huayu Capsules on cerebral ischemia reper-fusion injury rats may be related to Notch1/GAP-43 pathway.%目的：探讨参芎化瘀胶囊对全脑缺血再灌注大鼠海马区Notch1/GAP-43表达的影响。方法将100只健康雄性SD大鼠随机分为假手术组(n=25)、脑缺血再灌注组(n=25)、参芎化瘀胶囊低剂量组(n=25)以及高剂量组(n=25)。参芎化瘀胶囊低剂量组以及高剂量组灌胃剂量为240、480 mg/(kg·d),假手术组和脑缺血再灌注组按10 mL/kg体重给予蒸馏水,早上8：00给药,每日1次,连续7 d。运用改良的Pulsineli 4血管阻断(4-VO)法进行全脑缺血再灌注模型的制作,分别于1、2、3、7、14 d断头处死取海马组织,HE染色观察海马细胞形态变化,免疫组化法检测Notch1、GAP-43的表达。造模后1~3 d采用横木行走实验评价大鼠感觉运动功能。结果与假手术组比较,脑缺血再灌注组海马区正常神经元计数明显减少,差异有统计学意义(P<0.05),Notch1(术后1、2、3 d)、GAP-43(术后3、7、14 d)表达均增多,差异有统计学意义(P<0.05),横木行走实验评分明显减少(P<0.05)；与脑缺血再灌注组比较,参芎化瘀胶囊低剂量组正常神经元计数增多,Notch1、GAP-43蛋白明显增多(P<0.05),横木行走实验评分明显提高(P<0.05)。参芎化瘀胶囊高剂量组上述各指标变化表现得更加明显(P<0.05)。脑缺血再灌注组和参芎化瘀胶囊低剂量组中Notch1和GAP-43表达均呈正相关(r=0.838,P<0.01；r=0.786,P<0.01)。结论参芎化瘀胶囊可能通过Notch1/GAP-43通路对全脑缺血大鼠起神经保护作用。
展开▼
