摘要
目的探讨施万细胞相关功能蛋白:髓磷脂相关糖蛋白(MAG)、神经生长因子(NGF)、p75神经营养素受体(p75NTR)及神经细胞黏附分子(NCAM)在丙烯酰胺所致周围神经损伤及修复过程中的变化;通过比较坐骨神经和外周血中相关功能蛋白变化的相关性。方法 Wistar大鼠随机分为低(n=12)、中(n=12)、高(n=22)丙烯酰胺染毒组(7.5、15和20 mg/kg)和生理盐水对照组(n=22),腹腔注射染毒3周,建立周围神经损伤动物模型。染毒结束后,对照组及高剂量组中各留5只大鼠继续饲养4周,观察周围神经损伤后的恢复情况。Western blot法检测各组大鼠坐骨神经中MAG、p75NTR、NGF和NCAM蛋白的表达水平,ELISA法检测染毒期末及恢复期末血浆MAG的含量。结果 (1)丙烯酰胺染毒大鼠出现周围神经损伤体征且雌性动物更为显著,恢复4周后症状可缓解。(2)坐骨神经相关功能蛋白变化:与对照组比较,中、高剂量丙烯酰胺组MAG含量减少(P<0.05),恢复组MAG含量变化不显著;高剂量丙烯酰胺组的p75NTR含量较对照组显著升高(P<0.05),恢复组p75NTR含量略有上升,且在雌性组有统计学差异(P<0.05);NGF含量在雄性各染毒组间变化不显著,雄性恢复期染毒组大鼠NGF含量显著升高(P<0.05);雄性高剂量丙烯酰胺组的NCAM含量显著增加(P<0.05),雄性恢复期大鼠NCAM含量略有上升但无统计学差异;雌性大鼠各组中均未检测到NCAM及NGF的表达。(3)外周血相关功能蛋白变化:与对照组相比,高剂量染毒组大鼠血浆中MAG含量明显下降(P<0.05),恢复组MAG含量无明显变化。结论施万细胞4种功能蛋白的变化反映了丙烯酰胺致周围神经损伤及修复的功能状态;血浆中MAG含量变化与其在坐骨神经中的变化具有相关性。
Objective To explore the changes of four functional proteins which are related to Schwan cells (SCs) , including myelin-associated glycoprotein (MAG) , nerve growth factor (NGF) , p75 neurotrophin receptor (p75NTR) and neural cell adhesion molecule (NCAM) on damage and repair of peripheral nerve induced by acrylamide (Acr). From the changes of the protein level, some meaningful information for the mechanism of Acr neurotoxicity and the screening of biomarkers might be acquired. Methods Rats were administrated with Acr at dose of 7.5, 15 and 20 mg/kg by intraperitoneal injection for 3 weeks, high-dose group were observed for 4 weeks after 3 weeks exposure of Acr to create an animal model of peripheral nerve in injury and repair. Protein level of MAG, p75NTR, NGF and NCAM in rat sciatic nerve at the end of exposure and convalescent were measured by western blot. The level of MAG in plasma at the end of exposure and convalescent was measured by ELISA. Results (1) Rats treated with Acr appeared peripheral nerve damage symptom and began to recover after 4 weeks. The abnormal symptoms in female group were heavier than that of males, especially the high dose group. (2) Compared with the control group, the level of MAG decreased in the medium dose group and high dose group (P 〈0.05), the level of p75NTR increased in high dose group (P 〈 0. 05 ). There were no significant changes in the level of NGF between the control group and treated groups of male rats. Compared with the male control group, the level of NCAM in the the high dose group increased (P 〈 0.05). (3) Compared with the control group, the level of plasma MAG in the high dose group decreased (P 〈 0.05 ), while that in the recovery group was slightly increased. Conclusion The changes of those functional proteins may reflect the state of the peripheral nerve damage induced by Acr. The downregulation of MAG in rat plasma may be related with that in sciatic nerve.
出处
《卫生研究》
CAS
CSCD
北大核心
2014年第6期911-916,共6页
Journal of Hygiene Research
基金
国家自然科学基金(No.30901219
81273110)