小檗碱对糖尿病大鼠外周神经功能及神经病理性痛的影响

Effects of berberine on peripheral nerve function and neuropathic pain in diabetes rats

目的探讨小檗碱(Berberine,Ber)对糖尿病(DM)大鼠外周神经功能和神经病理性痛的影响及其作用机制。方法以链脲佐菌素(STZ)腹腔注射诱导形成DM模型,随机分成对照组、模型组和Ber组,其中Ber组给予187.5 mg/kg的Ber灌胃。用机械刺激法、热板法,分别测缩足反应阈值(MWT)、热痛阈值(HPT);电刺激诱导动作电位法测定坐骨神经传导速度(NCV);光镜观察脊髓组织形态学改变;用硝酸还原法、化学比色法测定一氧化氮(NO)、一氧化氮合酶(NOS)含量或活性。结果 DM大鼠MWT、HPT均明显降低(P<0.01),坐骨神经NCV明显减慢(P<0.05),脊髓背角萎缩,神经元变性坏死,核仁消失,尼氏小体消失,Ber组则明显恢复;DM大鼠血清、坐骨神经NO、NOS均明显减少(P<0.01),Ber组则明显升高(P<0.05)。结论 Ber能减轻DM大鼠神经病理性疼痛症状,维持外周神经的结构和功能,这种作用与其增加NOS活性,促进NO的合成和释放,抑制NO的灭活有关。

Objective To explore the possible mechanisms of berberine on peripheral nerve function and neuropathic pain in diabetes rats. Methods Adult male SD rats were randomly divided into 3 groups： normal, diabetes mellitus （ DM）, berberine （ 187.5 mg/kg） groups. The DM rat models were i.p. injected with 1% STZ for 2 weeks, the rats were treated for 8 weeks respectively with berberine. Mechanism withdraw threshold （MWT）, heat pain threshold （HPT）, sciatic nerve conduction velocity （NCV）, histopathological changes of the spinal cord, nitric oxide （NO） content and nitric oxide synthase （NOS） activity in serum and sciatic nerve were determined respectively. Results The NO content and NOS activity in serum and sciatic nerve of DM group were significantly lower than those of normal group （P 〈 0.05 or P 〈0.01 ） , but in berberine group, the above changes were reversed, there were significant differences compared with DM group （ P 〈 0. 05 or P 〈 0. 01 ）. Conclusions Berberine can reduce the symptoms of neuropathic pain in DM rats, preserve structure and function of peripheral nerve. Its mechanisms may be increasing NOS activity, promoting synthesis and release of NO, inhibiting inactivation of NO.