摘要
目的观察痰火方改善脑缺血大鼠脑灌注,保护神经胶质细胞的作用及机制。方法采用大脑中动脉线栓法建立脑缺血大鼠模型。按照随机数字表法将雄性SD大鼠分为假手术组、模型组、痰火方高剂量组(3.68 g/kg)、痰火方中剂量组(1.84 g/kg)、痰火方低剂量组(0.92 g/kg)及金纳多组(0.06 g/kg)。采用神经功能缺损评分评价神经功能缺损症状,磁共振T2加权成像(T2WI)检测脑缺血大鼠梗死体积,三维时间飞跃(3D-TOF)磁共振血管成像(MRA)观察大鼠颅内血管信号,动脉自旋标记(ASL)分析损伤脑区血流灌注的变化,神经元特异性核蛋白(NeuN)、少突胶质细胞标志蛋白2′3′-环核苷酸3′-磷酸二酯酶(CNPase)免疫荧光染色分别检测神经元、少突胶质细胞损伤。结果与模型组比较,痰火方高剂量组大鼠脑缺血24、48、72 h神经功能缺损评分降低(P<0.05,P<0.01),痰火方中、低剂量组及金纳多组大鼠脑缺血48、72 h神经功能缺损评分降低(P<0.05)。与模型组比较,痰火方高剂量组大鼠梗死体积缩小(P<0.05)。与假手术组比较,模型组大鼠右前动脉、右前交通动脉相对血管信号降低(P<0.01)。与模型组比较,痰火方高、中、低剂量组及金纳多组大鼠右前交通动脉相对血管信号增强(P<0.01)。与模型组比较,金纳多组大鼠梗死灶区相对脑血流量(rCBF)增高(P<0.05),痰火方各剂量组及金纳多组大鼠梗死灶边缘区rCBF增高(P<0.01)。免疫荧光染色结果显示:与假手术组比较,模型组大鼠梗死灶周围皮层NeuN、CNPase阳性表达降低(P<0.05,P<0.01)。与模型组比较,痰火方高剂量组及金纳多组大鼠梗死灶周围皮层NeuN、CNPase阳性表达升高(P<0.05,P<0.01),痰火方中剂量组大鼠梗死灶周围皮层CNPase阳性表达升高(P<0.05)。结论痰火方可改善脑缺血大鼠神经功能缺损症状,缩小梗死体积,改善脑灌注,减轻神经元、少突胶质细胞损伤。
Objective To observe the pharmacological effects and mechanism of Tanhuo Formula(THF)on protecting neuroglial cells and improving cerebral perfusion in rats with cerebral ischemia.Methods Cerebral ischemia model was induced by right middle cerebral artery occlusion.Rats were randomly divided into sham group,model group,three THF groups(high-dose:3.68 g/kg,mid-dose:1.84 g/kg,low-dose:0.92 g/kg),and ginaton group(0.06 g/kg)by using random sequence table.Neurological deficit score was used to evaluate the degree of neurological deficit in cerebral ischemia rats.T2-weighted imaging(T2 WI)was used to measure the infarct volume in cerebral ischemia rats.Three-dimensional time-of-flight magnetic resonance angiography(3 D-TOF MRA)was used to observe intracranial vascular signals in rats.Arterial spin labeling(ASL)was used to analyze the changes of blood perfusion in injured brain regions.Neuronal specific nuclear protein(NeuN)and 2′3′-cyclic nucleotide 3′-phosphodiesterase(CNPase)immunofluorescence staining were used to observe the damage to neurons and oligodendrocytes.Results Compared with the model group,the neurological deficits scores of rats in the high-dose THF group with cerebral ischemia for 24,48 and 72 h were reduced(P<0.05,P<0.01);the scores of neurological deficits of rats in the mid-dose and low-dose THF groups were also lower than those in the model group with cerebral ischemia for 48 and 72 h(P<0.05).Compared with the model group,the infarct volume of rats in the THF high-dose group was reduced(P<0.05).Compared with the sham group,the right anterior cerebral artery(ACA)and the right anterior communicating artery(AComA)signals in the model group were lower(P<0.01).compared with the model group,the relative signal intensity of the right side of the AComA in each treatment group and ginaton group was enhanced(P<0.01).Compared with the model group,the relative cerebral blood flow(rCBF)in the infarct of the rats increased in the ginaton group(P<0.05),while rCBF in the cortext surrounding the infarct increased in the three THF groups and ginaton group(P<0.01).Immunofluorescence staining results showed that the positive expressions of NeuN and CNPase in the cortex surrounding the infarct of the model group were lower than those in the sham group(P<0.05,P<0.01);the positive expressions in the cortex surrounding the infarct of NeuN and CNPase in the high-dose THF group and ginaton group were higher than those in the model group(P<0.05,P<0.01);Mid-dose THF also increased the positive expression of CNPase in the cortex surrounding the infarct(P<0.05).Conclusion THF can improve the symptom of neurological deficits,reduce the volume of infarction,increase the cerebral perfusion,protect neuron and oligodendrocytes from injury in rats with cerebral ischemia.
作者
李明聪
赵婷
赵晖
冯雪枫
陆允
杨乐
詹宇
高利
Li Mingcong;Zhao Ting;Zhao Hui;Feng Xuefeng;Lu Yun;Yang Le;Zhan Yu;Gao Li(School of Chinese Medicine,Capital Medical University,Beijing 100069,China;Xuanwu Hospital of Capital Medical University,Beijing 100053,China)
出处
《北京中医药大学学报》
CAS
CSCD
北大核心
2021年第7期605-614,共10页
Journal of Beijing University of Traditional Chinese Medicine
基金
北京市科学技术委员会“十病十药”研发专项(No.Z171100001717012)。
关键词
痰火方
脑缺血
侧支循环
神经元
少突胶质细胞
大鼠
Tanhuo Formula
cerebral ischemia
collateral circulation
neurons
oligodendrocytes
rats
