糖尿病周围神经病理性疼痛小鼠脊髓组织SGK1、CREB、IL-17的表达及机制
Expression of SGK1,CREB,and IL-17 in spinal cord tissues of mice with diabetic peripheral neuropathy pain and its mechanism
钟世奇 1黄媛馨 1沃春新 1王林1
作者信息
- 1. 贵州医科大学附属医院疼痛科,贵州贵阳 550004
- 折叠
摘要
目的 探讨糖尿病周围神经病理性疼痛(DPNP)模型小鼠脊髓组织中血清和糖皮质激素诱导激酶1(SGK1)、环磷腺苷效应元件结合蛋白(CREB)及白细胞介素17(IL-17)的表达及其可能的机制.方法 取4周龄健康雄性C57BL/6小鼠为正常(N)组(n=10)、4周龄雄性糖尿病基因突变小鼠(C57BL/KS db/db小鼠)为糖尿病模型组(n=40),糖尿病模型组小鼠分为神经痛(NP)组和糖尿病(DB)组,各组小鼠喂养8周;于实验第4、5、6、7及8周时,检测各组小鼠的随机血糖及热缩足潜伏期;于第8周时,处死小鼠,取脊髓组织,采用Western blot法和免疫荧光法检测脊髓组织中SGK1、CREB蛋白表达和IL-17水平.结果 DB组和NP组小鼠同时点随机血糖均较N组升高(P＜0.05),DB组和NP组小鼠第5～8周随机血糖均较同组第4周升高(P＜0.05);NP组小鼠第8周热缩足潜伏期较N组和DB组缩短(P＜0.05),NP组小鼠第8周热缩足潜伏期较第4周降低(P＜0.05);各组小鼠脊髓SGK1、CREB蛋白表达及IL-17荧光强度均有差异(P＜0.05),且表现为N组＜DB组＜NP组(P＜0.05).结论 DPNP模型小鼠脊髓组织SGK1、CREB及IL-17的表达增加,其机制可能与SGK1/CREB通路上调IL-17有关.
Abstract
Objective To explore the expression and mechanisms of serum and glucocorticoid induced kinase 1(SGK1),cyclic phosphoadenosine effector element-binding protein(CREB),and interleukin 17(IL-17)in spinal cord tissue of diabetic peripheral neuropathic pain(DPNP)model.Methods Four-week-old healthy male C57BL/6 mice were treated as normal(N)group(n=10)and 4-week-old male diabetic mutant mice(C57BL/KS db/db)were selected as the diabetic model group(n=40).Mice in the diabetes model group were divided into neuralgia(NP)and diabetic(DB)groups,and each group was fed for 8 weeks.At the 4,5,6,7 and 8 weeks,random blood glucose and heat shrinkage foot latency were detected in each group.At week 8,mice were killed,and spinal cord tissues were harvested.SGK 1,CREB protein expression and IL-17 levels in spinal cord tissues were determined by Western blot and immunofluorescence.Results The random blood glucose levels of both DB and NP groups were higher than those of the N group at the same time point(P＜0.05),and mice in DB and NP group increased from 5 to 8 weeks compared with week 4 of the same group(P＜0.05).The latency of heat shrink foot was shortened at week 8 in the NP group compared with the N and DB groups(P＜0.05).The latency of heat retraction in the mice of NP group was decreased at week 8 compared with week 4(P＜0.05).SGK1,CREB protein expression and IL-17 fluorescence intensity were different in each groups(P＜0.05),and N group＜DB group＜NP group(P＜0.05).Conclusion The expression of SGK1,CREB,and IL-17 in the spinal cord tissues of the DPNP model mice increases,which may be part of the pathogenesis of DPNP.
关键词
白细胞介素17/脊髓/小鼠/糖尿病周围神经病理性疼痛/血清和糖皮质激素诱导激酶1/环磷腺苷效应元件结合蛋白Key words
interleukin 17/spinal cord/mice/diabetic peripheral neuropathic pain/serum and glucocorticoid-induced kinase 1/cyclophospadenosine effector element-binding protein引用本文复制引用
基金项目
国家自然科学基金(82060811)
贵州省科技计划项目(黔科合基础-ZK[2021])
出版年
2024
NETL
NSTL
万方数据