糖尿病大鼠周围神经病变时神经电生理及病理的变化与通络方剂干预的作用

Electrophysiologic and pathologic changes in diabetic peripheral neuropathy rats and interventional effects of Tongluo recipe

目的探讨糖尿病大鼠周围神经病变(DPN)时神经电生理改变与病理变化的关系以及神经电生理、病理检查对DPN诊断的意义,同时评价通络方剂干预治疗的效果。方法24只健康雄性Sprague-Dawley大鼠经链脲佐菌素一次性腹腔注射方法诱导成DPN模型后,随机分为模型组和大(2.0g/kg通络方剂灌胃8周)、小(0.5g/kg通络方剂灌胃8周)剂量药物治疗组,另设正常对照组。8周后检测尾神经运动神经传导速度(MCV)、感觉神经传导速度(SCV)及潜伏期、神经电位波幅的变化,并测定病理定量指标。结果运动传导指标:与正常对照组比较,模型组的潜伏期显著延长(P<0.01),MCV显著减慢(P<0.01),电位波幅显著下降(P<0.05);而大、小剂量药物治疗组以上指标均较模型组显著改善(P值分别<0.05、0.01)。感觉传导指标:与正常对照组比较,模型组的潜伏期显著延长(P<0.01),SCV显著减慢(P<0.01),电位波幅显著下降(P<0.05);而大、小剂量药物治疗组以上指标均较模型组显著改善(P值分别<0.05、0.01);与小剂量药物治疗组比较,大剂量药物治疗组的潜伏期显著缩短(P<0.05),SCV显著加快(P<0.05)。图像定量分析:与正常对照组比较,模型组有髓纤维阳性面积、髓鞘面积及轴突面积均显著减小(P值均<0.01);与模型组比较,大、小剂量药物治疗组有髓纤维阳性面积、髓鞘面积及轴突面积均显著增大(P值均<0.01);与小剂量药物治疗组比较,大剂量药物治疗组的有髓纤维阳性面积、髓鞘面积均显著增大(P值分别<0.05、0.01)。结论有髓纤维阳性面积、髓鞘面积是反映DPN病程、疗效的更敏感的病理指标;SCV与髓鞘病理改变关系密切,可作为临床首选诊断DPN的电生理检测项目,但对亚临床或经足量药物治疗DPN的髓鞘病变敏感性尚存在不足。通络方剂对周围神经电生理、病理指标均有不同程度的改善,对于DPN有较好的治疗作用,大剂量效果优于小剂量。

Objective To investigate the relationship between electrophysiology and pathology changes in diabetic peripheral neuropathy （DPN） rats, so as to assess the value of electrophysiology and pathology in diagnosis of DPN, and to analyze the interventional effects of Tongluo recipe in treatment of DPN. Methods Twenty-four healthy male SD rats were intraperitoneally injected with a single dose of streptozotocin to induce DPN model and the rats were subsequently divided into 3 groups, namely, the DPN model group, the high dose Tongluo composite recipe （TLCR） group, and the low dose TLCR group. Rats in the latter 2 groups were lavaged once per day with 2.0 g/kg and 0.5 g/kg TLCR for 8 weeks, respectively. Another 8 healthy rats were taken as normal controls. The motor conduction velocity （MCV）, sensory conduction velocity （SCV）, potential latency and amplitude of caudal nerves were measured in all rats 8 weeks later. Morphometric quantitative analysis was also performed. Results Compared with the normal control group, MCV （ P〈0.01 ）, SCV （P〈0.01） and potential amplitude （P〈0.05） of the caudal nerve in the DPN model group were decreased, and the potential latency was increased （P〈0.01）. After TLCR treatment, the above indices were significantly improved and were close to those of the normal control group. There was no significant difference in SCV between the high dose group and the normal control group （P〉0.05）. SCV of the low dose group was significantly lower than that of normal control group （P〈0.05） and the high dose group （P〈0.05）. Morphometric quantitative analysis showed that the myelinated nerve fiber positive area, myelin sheath area and axon area in the DPN model group were smaller than those in the normal control group; the areas in the treatment groups were significantly increased compared with the DPN model group. Compared with the low dose group, the high dose group had significantly larger myelinated nerve fiber positive area and myelin sheath area, but not axon area. The changes of myelinated nerve fiber positive area and myelin sheath area were basically consistent with SCV changes in all groups, but the myelin sheath area of the high dose group was still smaller than that of the normal control group （P〈0.05）. Conclusion Myelinated nerve fiber positive area and myelin sheath area are more sensitive markers for the course and therapeutic outcome of DPN. SCV is closely related to the pathological changes of myelin sheath and can be the first choice among all electrophysiological indices for clinical diagnosis of DPN, but should be reserved for patients with subclinical DPN and those who have received high dose drug treatment. Tongluo recipe can improve the electrophysiological indices and ameliorate morphology abnormalities in peripheral myelinated nerve fibers. It has therapeutic effects on DPN and higher dose might have greater improvement. （Shanghai Med J, 2009, 32.. 410-413~）