脑源性神经营养因子对丙烯酰胺短期重复剂量神经损伤的体内干预研究

Study on effects of brain-derived neurotrophic factor in acrylamide-induced subacute neurotoxicity in vivo

目的在体内实验条件下探讨脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)对丙烯酰胺(acrylamide,ACR)所致神经损伤的干预效应。方法 30只雌性Wistar大鼠随机分为生理盐水对照组、BDNF对照组(48μg/kg BDNF)、30 mg/kg ACR染毒组(腹腔注射,1次/d,6 d/周,3周)和低、高剂量BDNF干预组(12和48μg/kg BDNF,尾静脉注射,1次/2 d,自第2周始);染毒步态评分、后肢撑力试验评价神经行为改变;检测脑分区、脊髓、坐骨神经及神经外重要的组织脏器的病理改变;ELISA法检测血浆BDNF的含量。结果 BDNF高剂量(48μg/kg)干预组对ACR所致大鼠神经损伤具有一定的保护作用,BDNF高剂量干预组与ACR单独染毒组比较,对于实验动物的神经系统具有一定的保护作用,如试验结束时体重高于ACR染毒组,异常体征弱于ACR染毒组,步态评分显著低于ACR染毒组,后肢撑力距离较ACR染毒组缩短,血浆BDNF含量高于ACR染毒组(P<0.05)小脑皮质空泡略少于ACR染毒组。所检测的神经外重要组织脏器未见明显的病理组织学异常。结论适当剂量外源性BDNF干预在实验动物水平对ACR所致短期重复剂量神经毒效应发挥一定的保护作用。

Objective This study was aimed to investigate the effects of brain-derived neurotrophic factor （BDNF） on acrylamide （ACR）-induced neurotoxicity in rats. Methods 30 Wi^tar rats were randomized as normal saline control, BDNF control （48 μg/kg BDNF）, 30 mg/kg ACR treatment group （intraperiioneal injection, one time each day, six days one week for 6 weeks） and two concentrations of BDNF （12 and 48 μg/kg, iv, one time every two days, start from the second week） intervention groups. The neurological changes were observed. Pathological changes of brain, spinal cord, sciatic nerve and other important organs or tissues of the body. Plasma level of BDNF was measured by ELISA kit. Results BDNF （48 μg/kg） administration significantly reduced the loss of body weight （P 〈 0. 05）, mitigated gait abnormalities （ P 〈 0. 05 ） and pathological changes of cerebellar induced by 30 mg./kg ACR. No significant pathological changes were found in other tested organs or tissue. Plasma level of 48 μg/kg BDNF intervention group was higher than that of the ACR treatment group （P 〈0. 05）. Conclusion In conclusion, BDNF with appropriate doses had protective effects to some extent on ACR-induced subactue neurotoxicity in rats.