醛糖还原酶抑制剂对实验性糖尿病周围神经病大鼠内源性NGF水平及生理功能的影响

The Effect of Aldose Reductase Inhibitor(ARI) on Endogenous NGF and Physiological Functions in Rats with Experimental Diabetic Neuropathy

目的探讨神经生长因子(NGF)在糖尿病周围神经病(DNP)发病中的作用以及醛糖还原酶抑制剂(ARI)改善生理功能和NGF水平的作用机制。方法采用链脲佐菌素(STZ)制成大鼠DNP模型后给予ARI治疗,检测大鼠治疗前后摇尾阈值、神经电生理和血清及坐骨神经NGF水平,并与DNP模型组和健康对照组相比较。结果与健康对照组比较,DNP模型大鼠摇尾阈值升高[(49.56±0.32)℃ vs.(47.60±1.37)℃,P<0.05],运动神经传导速度(MNCV)和感觉神经传导速度(SNCV)均下降[(32.82±2.96)m/s vs.(52.76±6.52)m/s,P<0.05;(39.22±8.15)m/s vs.(45.33±8.21)m/s,P<0.05],血清和坐骨神经中NGF水平下降[分别为(154.82±136.18)pg/mL vs.(313.71±156.99)pg/mL,P<0.05;(457.40±187.59)pg/mL vs.(688.93±1 6 7.85)pg/mL,P<0.05]。经ARI治疗后大鼠摇尾阈值显著低于DNP模型组(P<0.05),SNCV、血清及坐骨神经中NGF水平均显著高于DNP模型组(P<0.05),同时经ARI治疗后其摇尾阈值较治疗前显著降低,SNCV、MNCV较治疗前显著增高(P<0.05)。结论 NGF表达或运输水平下降在DNP发病中具有作用。ARI可促进NGF的表达并改善热痛觉和神经传导速度。

Objective To investigate the role of nerve growth factor （NGF） in the pathogenesis of diabetic neuropathy （DNP） and the effect of atdose reductase inhibitor （ARI） on the physiological functions and the level of NGF. Methods After the interference of administered streptozotoein （STZ）, DNP rats were treated with ARI, we measured the tail-flick threshold, electrophysiologic changes of nerves and the contents of NGF in serum and sciatic nerve, then compared with those of untreated STZ induced DNP rats and the normal controls. Results Compared with the normal controls, the tail-flick threshold elevated [ （49.56±0.32）℃ vs. （47.60±1.37）℃, P〈0.05], the NCV decreased [（32.82±2.96） m/s vs. （52.76 ± 6.52） m/s of MNCV, P〈0. 05） ; （39.22 ± 8.15） m/s vs. （45.33±8.21） m/s of SNCV, P〈0. 05）] and the contents of NGF in serum and sciatic nerve decreased significantly [（154.82±136.18） pg/mL vs. （313.71±156.99） pg/mL of serum, P〈0.05）; （457.40 ±187.59） pg/mL vs. （688.93± 167.85） pg/mL of sciatic nerve, P〈0.05,respectively] in DNP model rats. The treatment with ARI significantly improved them （P〈0.05）. Compared with DNP model rats, the tail-flick threshold decreased, the SNCV and the contents of NGF in serum and sciatic nerve elevated in the treatment group rats. The.tail-flick threshold decreased significantly compared with before treatment, the SNCV and MNCV elevated significantly compared with before treatment. Conclusions The decrease of production of NGF may contribute to the occurrence of DNP. ARI can promote the production of endogenous NGF and improve the thermal pain and NCV in rats.