神经生长因子对2,5-己二酮中毒大鼠周围神经损伤的治疗作用

Therapeutic effect of mouse nerve growth factor ontoxic neuropathy induced by 2,5-hexanedione in rats

目的 观察鼠源性神经生长因子 (mNGF)对2 ,5 己二酮中毒大鼠周围神经病的治疗效果。方法采用 2 ,5 己二酮 4 5 0mg·kg- 1·d- 1ig染毒 ,通过对姿势、步态、前后肢肌力的体征评分、坐骨神经运动神经传导速度 (MNCV)测定和神经病理检查 ,证实制成 2 ,5 己二酮中毒大鼠周围神经病模型 ,而后将相同周围神经体征评分的中毒大鼠 2 6只随机分为mNGF治疗组与染毒未治组进行疗效比较。结果染毒组大鼠于染毒 2 5d体征评分显示 ,中度与重度周围神经损伤者约占总数的 92 % ;坐骨神经MNCV比对照组明显减慢 ;神经病理检查发现 ,胫神经部分神经纤维轴索变性。经mNGF 30 μg·kg- 1·d- 1im治疗 2 1d后 ,治疗组大鼠的姿势、步态与前后肢肌力的恢复情况显著优于染毒未治组。结论 mNGF能显著加速 2 ,5 己二酮中毒性周围神经病的恢复 ,为临床应用mNGF治疗正己烷中毒性周围神经病提供了动物实验依据。

AIM To investigate the therapeutic effect of m ouse nerve growth factor (mNGF) on toxic neuropathy induced by 2,5-hexanedione, a known neurotoxic metabolite of n-hexane in rats. METHODS 2,5- Hexanedione 450 mg·kg -1·d -1 was administered ig for 25 d. Neurolog ic deficits were evaluated by scoring of neuropathic signs (gesture, gait and mu scular strength abnormalities), motor nerve conduction velocity (MNCV) detection and neuropathologic observation. Rats with verified toxic neuropathy were treat ed with mNGF 30 μg·kg -1·d -1 im for 21 d. RESULTS Nin ety two percent of the rats exposed to 2,5-hexanedione developed moderate or se vere neuropathic signs, and their mean MNCV decreased significantly in comparis on with that of the control group. Neuropathological observation on tibial nerve fibers by electron-microscopy confirmed the existence of axonal degeneration. After treatment by mNGF, the rats showed significant improvements of neuropathic signs in comparison with the untreated poisoned group. CONCLUSION mNGF accelerates the recovery of 2,5-hexanedione-induced neuropathy,providing evidence and suggesting rationale for clinical application of mNGF in treating patients with n-hexane neuropathy.