益消方对糖尿病周围神经病变小鼠的神经保护作用研究

Neuroprotective effect of Yixiao decoction on diabetic peripheral neuropathy in mice

目的探讨益消方对糖尿病周围神经病变小鼠坐骨神经的保护作用。方法选取24只8周龄KKAy小鼠完全随机分为模型组、硫辛酸组、益消方组,每组8只,并以8只同周龄C57BL/6J小鼠作为对照组。硫辛酸组给予硫辛酸60 mg/(kg·d)灌胃,益消方组给予益消方7.7 g/(kg·d)灌胃,对照组及模型组给予同容积的蒸馏水灌胃。每天给药1次,连续12周。比较各组小鼠干预前及干预第4、8、12周的空腹血糖、体重和神经功能等。结果模型组、硫辛酸组、益消方组干预第8、12周空腹血糖和体重均高于对照组(均P<0.05)。硫辛酸组干预第12周空腹血糖低于模型组;益消方组干预第8、12周空腹血糖和体重均低于模型组;益消方组干预第12周体重低于硫辛酸组(均P<0.05)。模型组、硫辛酸组、益消方组干预前和干预第8、12周机械痛阈值均低于对照组(均P<0.05)。模型组、硫辛酸组、益消方组干预前和干预第4、8、12周甩尾时间均长于对照组(均P<0.001)。硫辛酸组和益消方组干预第8、12周机械痛阈值均高于模型组,干预第4、8、12周甩尾时间均短于模型组;益消方组干预第12周机械痛阈值高于硫辛酸组[(2.54±0.24)g比(1.95±0.28)g],干预第4、8、12周甩尾时间均短于硫辛酸组(均P<0.001)。结论益消方可减轻糖尿病周围神经病变小鼠坐骨神经损伤,其机制可能与调节Keap1-Nrf2-ARE信号通路及下游超氧化物歧化酶、过氧化氢酶的表达有关。

Objective To investigate the protective effect of Yixiao decoction on sciatic nerve in mice with diabetic peripheral neuropathy.Methods Twenty-four KKAy mice aged 8 weeks were completely random divided into model group,lipoic acid group and Yixiao decoction group,with 8 mice in each group.Eight C57BL/6J mice of the same age were used as the control group.The lipoic acid group was given lipoic acid 60 mg/(kg·d)by gavage,the Yixiao decoction group was given Yixiao decoction 7.7 g/(kg·d)by gavage,and the control and model groups were given distilled water by gavage.The drug was administered once daily for 12 weeks.The fasting blood glucose,body weight and neurological function of mice in each group were compared before and 4,8,12 weeks after intervention.Results The fasting blood glucose and body weight of the model group,lipoic acid group and Yixiao decoction group were higher than those of the control group at 8 and 12 weeks after intervention(all P<0.05).The fasting blood glucose of the lipoic acid group was lower than that of the model group at 12 weeks after intervention.The fasting blood glucose and body weight of the Yixiao decoction group were lower than those of the model group at 8 and 12 weeks after intervention.The body weight at 12 weeks after intervention in the Yixiao decoction group was lower than that in the lipoic acid group(all P<0.05).The mechanical pain thresholds of the model group,the lipoic acid group and the Yixiao decoction group were lower than those of the control group at before and 8,12 weeks after intervention(all P<0.05).The tail flick times of before and 4,8,12 weeks after intervention in the model group,lipoic acid group and Yixiao decoction group were higher than those in the control group(all P<0.001).The mechanical pain thresholds of the lipoic acid group and the Yixiao decoction group were higher than those of the model group at 8 and 12 weeks after intervention,and the tail flick times of the lipoic acid group and the Yixiao decoction group were lower than those of the model group at 4,8 and 12 weeks after intervention.The mechanical pain threshold at 12 weeks after intervention in the Yixiao decoction group was higher than that in the lipoic acid group[(2.54±0.24)g vs(1.95±0.28)g],and the tail flick times at 4,8 and 12 weeks after intervention were lower than those in the lipoic acid group(all P<0.001).Conclusion Yixiao decoction can reduce sciatic nerve injury in mice with diabetic peripheral neuropathy,and its mechanism may be related to the regulation of Keap1-Nrf2-ARE signaling pathway and the downstream expression of superoxide dismutase and catalase.