莫诺苷调控糖尿病周围神经病变大鼠坐骨神经氧化应激损伤的机制  

Mechanism of Morroniside regulating oxidative stress injury of sciatic nerve in diabetic peripheral neuropathy rats

作　　者：邓小兰 那丽莎 于雪 张凯 曲娜 DENG Xiaolan;NA Lisha;YU Xue;ZHANG Kai;QU Na(Department of Pharmacy,Shuangliu Maternal and Child Health Hospital,Sichuan Province,Chengdu 610299,China;Department of Pharmacy,Hongqi Hospital Affiliated to Mudanjiang Medical University,Heilongjiang Province,Mudanjiang157011,China)

机构地区：[1]成都市双流区妇幼保健院药学部,四川成都610299 [2]牡丹江医学院附属红旗医院药学部,黑龙江牡丹江157011

出　　处：《中国当代医药》2024年第18期4-8,共5页China Modern Medicine

基　　金：黑龙江省中医药管理局中医药科研课题(ZHY2022-042)。

摘　　要：目的探讨莫诺苷对糖尿病周围神经病变(DPN)大鼠坐骨神经氧化应激损伤的影响。方法48只大鼠分为对照组、DPN组、莫诺苷组、莫诺苷+Brusatol组,每组12只。检测空腹血糖、机械痛阈值、热痛阈值、坐骨神经传导速度的变化;透射电镜观察坐骨神经超微结构变化;ELISA法检测坐骨神经中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性;Western blot检测坐骨神经中核因子E2相关因子2(Nrf2)、沉默信息调节因子2相关酶1(SIRT_(1))、叉头转录因子o3(Foxo3)蛋白。结果DPN组、莫诺苷组、莫诺苷+Brusatol组坐骨神经髓鞘受损,空腹血糖、热痛阈值、坐骨神经中IL-6、TNF-α、MDA含量高于对照组,机械痛阈值、感觉和运动神经传导速度、坐骨神经中SOD活性及Nrf2、SIRT_(1)、Foxo3蛋白低于对照组,差异有统计学意义(P<0.05);莫诺苷组坐骨神经组织超微结构损伤改善,空腹血糖、热痛阈值、坐骨神经中IL-6、TNF-α、MDA含量低于DPN组,机械痛阈值、感觉和运动神经传导速度、坐骨神经中SOD活性及Nrf2、SIRT_(1)、Foxo3蛋白表达高于DPN组,差异有统计学意义(P<0.05);在莫诺苷组基础上给予Nrf2抑制剂Brusatol后,莫诺苷的保护作用被逆转。结论莫诺苷可能通过激活Nrf2/SIRT_(1)/Foxo3通路改善DPN大鼠坐骨神经氧化应激损伤。Objective To investigate the impacts of Morroniside on oxidative stress injury of sciatic nerve in diabetic peripheral neuropathy(DPN)rats.Methods A total of 48 rats were grouped into a control group,DPN group,Morroniside group,Morroniside+Brusatol group,each group consisted of 12 rats.The changes in fasting blood glucose,mechanical pain threshold,thermal pain threshold,and sciatic nerve conduction velocity were detected.Transmission electron microscopy observe the ultrastructural changes of the sciatic nerve.ELISA method detect the levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),malondialdehyde(MDA),and superoxide dismutase(SOD)activity in the sciatic nerve.Western blot detect nuclear factor erythroid 2 related factor 2(Nrf2),silent mating-type information regulation 2 homolog 1(SIRT_(1)),and forkhead box class o3(Foxo3)proteins in the sciatic nerve.Results Sciatic nerve myelin in DPN group,Morroniside group,Morroniside+Brusatol group were significantly damaged,fasting blood glucose,heat pain threshold,contents of IL-6,TNF-αand MDA in sciatic nerve were higher than those in control group,mechanical pain threshold,sensory and motor nerve conduction velocity,SOD activity in sciatic nerve and expression of Nrf2,SIRT_(1) and Foxo3 protein were lower than those in control group(P<0.05).The ultrastructural damage of sciatic nerve tissue in Morroniside group was improved,and the contents of fasting blood glucose,heat pain threshold,IL-6,TNF-αand MDA in sciatic nerve were lower than those in DPN group.The mechanical pain threshold,sensory and motor nerve conduction velocity,SOD activity and Nrf2,SIRT_(1),Foxo3 protein expression in sciatic nerve were higher than those in DPN group(P<0.05).The protective effect of Morroniside was reversed when Brusatol,an Nrf2 inhibitor,was given in addition to Morroniside group.Conclusion Morroniside may improve oxidative stress injury of the sciatic nerve in DPN rats by activating the Nrf2/SIRT_(1)/Foxo3 pathway.

关 键 词：莫诺苷 糖尿病周围神经病变 核因子E2相关因子2 沉默信息调节因子2相关酶1 叉头转录因子o3 坐骨神经 氧化应激 

分 类 号：R587[医药卫生—内分泌]