摘要
目的探讨芪归通络颗粒通过调控核因子E2相关因子2(Nrf2)/核因子(NF)-κB通路,改善糖尿病周围神经病变(DPN)的作用机制。方法雄性SD大鼠中随机选择10只作为空白组,其余大鼠用高脂饲料联合链尿佐菌素诱导DPN模型。造模成功后随机分为甲钴胺组、芪归组和模型组。予相应药物连续灌胃8周后,检测大鼠尾尖血糖水平、机械痛阈值(PWMT)和神经传导速度(MNCV);HE染色法观察大鼠坐骨神经病理学变化;ELISA法检测血清白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α、超氧化物歧化酶(SOD)、丙二醛(MDA)含量;Western blot和RT-qPCR法检测大鼠坐骨神经核因子B抑制蛋白α(IκBa)、NF-κB、Nrf2、Kelch样环氧氯丙烷相关蛋白1(Keap1)蛋白与mRNA表达。结果与空白组比较,模型组大鼠血糖、IL-6、TNF-α、MDA水平显著升高,SOD水平显著降低(P<0.05),PWMT和MNCV明显下降(P<0.05),坐骨神经Nrf2、IκBa蛋白及mRNA表达降低,NF-κBp65、Keap1蛋白及mRNA表达增加(P<0.01);与模型组比较,芪归组血糖水平明显下降,甲钴胺组和芪归组IL-6、TNF-α、MDA水平明显降低,SOD水平明显上升(P<0.05),PWMT和MNCV明显上升,坐骨神经Nrf2、IκBa蛋白及mRNA表达上升,NF-κB p65、Keap1蛋白及mRNA表达降低(P<0.05),坐骨神经病理形态改善明显。结论芪归通络颗粒可能通过调控Nrf2/NF-κB信号通路,减轻炎症反应、改善氧化应激损伤,从而提高DPN大鼠的神经传导速度。
Objective To investigate the mechanism of Qigui Tongluo granule in improving diabetic peripheral neuropathy(DPN)by regulating Nrf2/NF-κB pathway.Methods Ten male SD rats were randomly selected as the blank group,and the remaining rats were induced DPN model by high-fat diet combined with streptozotocin.After successful modeling,the rats were randomly divided into mecobalamin group,Qigui group and model group.After 8 weeks of continuous gavage for the corresponding drugs,the blood glucose level of tail tip,mechanical pain threshold(PWMT)and nerve conduction velocity(MNCV)of the rats were measured.The pathological changes of sciatic nerve were observed by HE staining.The serum levels of IL-6,TNF-α,SOD and MDA were detected by ELISA.Western blot and RT-qPCR were used to detect the protein and mRNA expressions of IκBa,NF-κB,Nrf2,and Keap1 in the sciatic nerve.Results Compared with the blank group,the blood glucose,IL-6,TNF-αand MDA in the model group were significantly increased,while SOD was significantly decreased(P<0.05),PWMT and MNCV were significantly decreased(P<0.05),and the expression of Nrf2 and IκBa protein and mRNA in the sciatic nerve was decreased,while the protein and mRNA expressions of NF-κBp65 and Keap1 were increased(P<0.01)in the model group.Compared with the model group,the blood glucose level was significantly decreased in the Qigui group,and IL-6,TNF-αand MDA were significantly decreased,while SOD was significantly increased in the mecobalamin and Qigui groups(P<0.05).PWMT and MNCV were significantly increased,and the expressions of Nrf2 and IκBa protein and mRNA in the sciatic nerve were increased,while the expressions of NF-κBp65 and Keap1 protein and mRNA were significantly decreased(P<0.05),and the morphology of sciatic nerve was significantly improved in the mecobalamin and Qigui groups.Conclusion Qigui Tongluo granule may improve the nerve conduction velocity of diabetic peripheral neuropathy rats by regulating Nrf2/NF-κB signaling pathway,reducing inflammatory reaction and improving oxidative stress injury.
作者
朱梦燕
方朝晖
李瑜璠
周鑫鑫
张银玉
尹样样
王胜茂
ZHU Mengyan;FANG Zhaohui;LI Yufan;ZHOU Xinxin;ZHANG Yinyu;YIN Yangyang;WANG Shengmao(The First Clinical Medical School of Anhui University of Chinese Medicine,Hefei 230012,China;The First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230013,China)
出处
《中国中医基础医学杂志》
2025年第8期1384-1388,共5页
JOURNAL OF BASIC CHINESE MEDICINE
基金
国家自然科学基金项目(82174153)
安徽省高校协同创新项目(GXXT-2020-025)
合肥综合性国家科学中心大健康研究院新安医学与中医药现代化研究所“揭榜挂帅”项目(2023CXMMTCM003)。
关键词
芪归通络颗粒
糖尿病周围神经病变
氧化应激
炎症
Qigui Tongluo granule
Diabetic peripheral neuropathy
Oxidative stress
Inflammation
