NF-κB在糖尿病性神经痛中的作用及机制  

Role of NF-κB in diabetic neuropathy

作　　者：黄阳亮[1] 钟祎[2] 胡景鑫[2] 

机构地区：[1]中山大学附属第一医院脊柱外科,广东广州510080 [2]广州医科大学生理教研室,广东广州510182

出　　处：《中国病理生理杂志》2014年第10期1784-1788,共5页Chinese Journal of Pathophysiology

基　　金：广东省自然科学基金博士启动基金资助项目(No.S2012040006843)

摘　　要：目的:探讨NF-κB在糖尿病神经痛中的作用及机制。方法:用腹腔注射链脲霉素(streptozocin,STZ)的方法复制大鼠糖尿病模型;痛行为学方法检测大鼠双侧后肢机械性撤足阈值和热撤足阈值;Western blotting方法检测大鼠脊髓L4和L5背根神经节(dorsal root ganglion,DRG)中p-NF-κB和t-NF-κB的表达。免疫组织化学方法检测抑制NF-κB对糖尿病性神经痛大鼠脊髓L4和L5 DRG中钠通道Nav1.7表达的影响。结果:注射STZ后第4周,大鼠双侧下肢机械性撤足阈值和热撤足阈值均明显下降,持续至术后12周;糖尿病性神经痛大鼠L4和L5DRG中p-NF-κB表达明显增加,鞘内注射NF-κB抑制剂PDTC可明显抑制糖尿病性神经痛大鼠L4和L5 DRG中p-NF-κB和Nav1.7的表达上调,大鼠后肢痛觉过敏现象也明显减轻。结论:L4和L5 DRG中p-NF-κB表达上调与糖尿病性神经痛的产生密切相关,抑制NF-κB活化可以阻断Nav1.7的表达上调并且改善大鼠痛觉过敏的症状。AIM： To investigate the role of NF-κB in diabetic neuropathy. METHODS： The diabetic rats were induced by intraperitoneal injection of streptozocin（ STZ）. The pain behavior test was used to detect the mechanical and thermal withdraw threshold of the rats＇ bilateral hind paws. The protein levels of p-NF-κB and t-NF-κB in the rats＇ L4 and L5 dorsal root ganglions（ DRG） were determined by Western blotting. The expression of Nav1. 7 in DRG of diabetic neuropathy rats with or without NF-κB inhibitor PDTC was detected by the method of immunohistochemistry. RESULTS：The mechanical and thermal withdraw threshold of bilateral hind paws in the diabetic rats was decreased from 4 weeks to 12 weeks after injection of STZ. The protein levels of p-NF-κB in L4 and L5 DRG were significantly increased in the rats with diabetic neuropathy. Intrathecal administration of NF-κB inhibitor PDTC attenuated the increase in p-NF-κB and Nav1. 7 in L4 and L5 DRG. Pain behaviors were also alleviated by PDTC. CONCLUSION： The increase in p-NF-κB is closely related to the generation of diabetic neuropathy. Inhibition of NF-κB blocks pain behaviors and the over-expression of Nav1. 7in DRG.

关 键 词：糖尿病性神经痛 NF-ΚB 电压门控性钠通道 背根神经节 

分 类 号：R338[医药卫生—人体生理学]