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

作　　者：钟世奇 黄媛馨 沃春新 王林 ZHONG Shiqi;HANG Yuanxin;WO Chunxin;WANG Lin(Department of Pain Management,the Affiliated Hospital Guizhou Medical University,Guiyang 550004,Guizhou,China)

机构地区：[1]贵州医科大学 [2]贵州医科大学附属医院疼痛科,贵州贵阳550004

出　　处：《贵州医科大学学报》2024年第8期1135-1140,共6页Journal of Guizhou Medical University

基　　金：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〕)。

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。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 

分 类 号：R619[医药卫生—外科学]