艾灸对血管性痴呆大鼠海马内VEGF、flt-1、bFGF及bFGF-r表达的影响

Effects of Moxibustion on the Expressions of Hippocampal VEGF,flt-1,bFGF,and bFGF-r in Vascular Dementia Rats

目的观察艾灸对血管性痴呆(vascular dementia,VD)大鼠海马内血管内皮生长因子(vascular endothelial growth factor,VEGF)、fam样酪氨酸激酶-1(fms-like tyrosine kinase-1,flt-1)、碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF),和碱性成纤维细胞生长因子受体(basic fibroblast growth factor receptor,bFGF-r)的表达水平的影响,研究灸法在治疗血管性痴呆中的促血管生成机制。方法选取Wistar雄性老年大鼠,双侧颈总动脉缺血再灌注-硝普钠注射法制备大鼠血管性痴呆模型,电脑随机数字表法随机分为3组:艾灸组、西药组、模型组,并设假手术组对照。艾灸组取百会、大椎、神庭穴艾灸治疗,西药组茴拉西坦灌胃,15天为1个疗程,均为2个疗程。神经行为学评分并结合跳台仪检测治疗前、第2疗程后学习记忆成绩;免疫组化检测各组大鼠海马VEGF、bFGF及其受体flt-1、bFGF-r的表达。结果经2个疗程治疗后,动物跳台实验的潜伏期、错误次数及神经行为学评分,艾灸组及西药组与模型组比较差异有统计学意义(P<0.01,P<0.05),艾灸组与西药组比较潜伏期及神经行为学评分差异也有统计学意义(P<0.05)。表明艾灸、西药在提高VaD大鼠潜伏期,降低VaD大鼠错误次数以及对神经行为学评分影响均有显著疗效,而艾灸组明显优于西药组(P<0.01,P<0.05)。艾灸组及西药组与模型组比,海马内表达VEGF、flt-1、bFGF的灰度值差异均有统计学意义,bFGF-r的表达仅艾灸组与模型组比较差异有统计学意义;VEGF、flt-1艾灸组与西药组比较差异有统计学意义(P<0.05)。结论艾灸在改善VD大鼠行为学评分及提高记忆成绩均有确切疗效,其作用机制可能存在着艾灸调控VD大鼠海马内VEGF、flt-1、bFGF和bFGF-r的表达水平,特别是上调关键因子VEGF、flt-1表达,促进了要害部位的血管生成,并最终激发了脑内神经的损伤修复机制。

Objective To observe the expression levels of hippocampal vascular endothelial growth factor （VEGF）, fms-like tyrosine kinase-1 （fit-1）, basic fibroblast growth factor （bFGF）, and basic fibroblast growth factor receptor （bFGF-r） in vascular dementia （VD） rats, thus studying the angiogenesis mechanism of moxi- bustion in VD. Methods Sixty male elderly Wistar rats were selected. The VD rat model was prepared by bilateral carotid artery occlusion and reperfusion of sodium nitroprusside injection. The model rats were divided into 3 groups by the random digit table, i. e., the moxibustion group, the Western medicine group, and the model group. A sham-operation control group was also set up. In the moxibustion group rats was acupunctured at Baihui （GV20）, Shenting （GV14）, and Dazhui （GV24）. Aniracetam was given to rats in the Western medicine group by gastrogavage for 2 therapeutic courses, 15 days as one course. The learning and memory results were observed by the neuroethological score in combination of step-down avoidance test before treatment and by the end of the 2nd course respectively. The expression levels of hippocampal VEGF, fit-1, bFGF, and bFGF-r of all rats were detected using immunohistochemical assay. Results After 2 courses of treatment, statistical difference existed in the latent period, the error times, and the neuroethological score in the moxibustion group and the Western medicine group when compared with the model group （P〈0.01, P〈0.05）. Statistical difference existed in the latent period and the neuroethological score between the moxibustion group and the Western medicine group （ P 〈 0.05）, which indicated that moxibustion and Western medicine showed significant effects in improving the latent period, decreasing the error times and the neuroethological score. Better results were obtained in the moxibustion group than in the Western medicine group （ P 〈0.01, P 〈0.05）. Statistical difference of the average grey level （AGL） of hippocampal VEGF, fit-1, and bFGF existed in the moxibustion group and the Western medi- cine group when compared with the model group. Statistical difference of the bFGF-r expression existed only be- tween the moxibustion group and the model group. Statistical difference of the VEGF and fit-1 expressions existed between the moxibustion group and the Western medicine group （ P 〈0.05）. Conclusions Moxibustion showed confirmative effects in improving the behavioral score and memory performance in VD rats. Its mechanisms might lie in that moxibustion regulated and controlled the expression levels of hippocampal VEGF, fit-1, bFGF, and bF- GF-r in VD rats. Particularly it up-regulated the expression levels of key factors VEGF and fit-1, promoted the angiogenesis in the vital parts, and ultimately stimulated the repairing mechanisms of cerebral nerve injury.