参芎滴丸对MCAO模型大鼠脑梗死体积及脑组织NF-κB表达的影响

Effects of Shenxiong Pill on Infarct Brain Volumes and NF-κB Expression in SD Rats with Middle Cerebral Artery Occlusion (MCAO)

目的观察传统中药制剂参芎滴丸对大脑中动脉闭塞(MCAO)模型大鼠脑梗死体积及脑组织核因子κB(NF-κB)表达的影响。方法采用线栓法制备大鼠MCAO模型,169只SD大鼠以是否接受造模和造模前药物干预,随机分为空白组、假手术组、模型组、环磷酰胺组(造模前8d,15mg/kg,1次/d灌胃)和参芎滴丸组,其中参芎滴丸组大鼠按参芎滴丸临床剂量1g/(kg·次)的20倍(高剂量组)、10倍(中剂量组)、5倍(低剂量组)灌胃(造模前8d,1次/d)。除空白组外,各组再以时间节点随机分为48h、72h两个亚组。处死大鼠后用图像处理软件计算脑梗死体积,脑组织常规HE染色观察病理学改变,免疫组化染色观察NF-κB的表达。结果参芎滴丸高、中、低剂量组及环磷酰胺组与模型组相比,48h、72h梗死体积缩小(P<0.05)。空白组、假手术组脑组织中未见NF-κB阳性细胞,大鼠缺血损伤48h、72h后模型组内梗死区NF-κB阳性细胞增多,同时NF-κB积分光密度也明显增高。与模型组相比,参芎滴丸低、中、高剂量组在缺血梗死48h、72hNF-κB阳性细胞数和积分光密度值减少,即NF-κB的表达下调,差异有统计学意义(P<0.05);参芎滴丸高、低剂量组组间相比差异也有统计学意义(P<0.05)。结论参芎滴丸能减小脑梗死体积,可抑制脑缺血模型大鼠脑组织的炎性反应,减轻脑组织的病理损伤,对神经元具有保护作用,其抑制NF-κB的表达可能是其作用机制之一。

Objective To investigate the effects of Shenxiong Pill on the infarct volume and expression of NF-κB in brains of rats with middle cerebral artery occlusion.Methods 169 SD rats were randomly divided into five groups：normal group,sham group,model group,cyclophosphamide group and Shenxiong Pill group.MCAO rat models were established by string ligation（for model,cyclophosphamide-treated and Shenxiong-treated groups）.Rats in the Shenxiong Pill group was further randomly divided into sub-groups,receiving a range of high dose treatment（5to 20 times of clinical dosage）.Brains of the rats were examined 48 hor 72hafter interventions in a random order.Image processing software was used in the calculation of volume of cerebral infarction.Conventional HE staining was used for observation of brain tissue.Immunohistochemical method was used to determine NF-κB expression.Results Compared with the model group,rats treated with Shenxiong Pill and cyclophosphamide had lower infarct brain volumes（P〈0.05）.NF-κB positive inflammatory cells were not found in the normal and sham groups.But the MCAO model rats had increased numbers of NF-κB positive inflammatory cells and higher integral optical density of NF-κB over time.Compared with the model group,lower numbers and expression of NF-κB positive inflammatory cells were found in those treated with Shenxiong Pill（P〈0.05）.Higher dosage of Shenxiong was associated with lower numbers and expression of NF-κB inflammatory cells（P〈0.05）.Conclusion Shenxiong Pill can reduce pathological damage to brains as a result of cerebral ischemia,possibly through inhibiting the expression and activation of NF-κB.