背根神经节Nav1.7在大鼠糖尿病神经病理性痛中的作用  

Role of Nasa in dorsal root ganglia in a rat model of diabetic neuropathic pain

作　　者：柯昌斌[1] 黄晓霞[2] 王燕[1] 刘菊英[1] 

机构地区：[1]湖北医药学院附属太和医院麻醉科,湖北省十堰市442000 [2]湖北医药学院附属太和医院肾病内科,湖北省十堰市442000

出　　处：《中华麻醉学杂志》2011年第8期947-949,共3页Chinese Journal of Anesthesiology

摘　　要：目的评价背根神经节（DRG）Nav1.7在大鼠糖尿病神经病理性痛中的作用。方法雌性Wistar大鼠32只，月龄3个月，体重180-220g。采用腹腔注射链脲菌素65mg／kg的方法制备糖尿病神经病理性痛模型。模型制备成功后第10天鞘内置管。采用随机数字表法，将大鼠随机分为4组（n=8），正常对照组（C组）：不做任何处理；假手术组（S组）：仅鞘内置管；糖尿病神经病理性痛（DNP组）：制备糖尿病神经病理性痛模型，并鞘内置管；Nav1.7阻断剂组（E组）：制备糖尿病神经病理性痛模型，鞘内置管后第4天鞘内注射Nav1.7阻断剂ProTx-Ⅱ10ttg／kg，DNP组和S组注射等容量生理盐水。于鞘内注射后1h测定机械缩足阈值（MWT）和神经传导速度（NCV），随后处死大鼠，取l4-6DRG，采用免疫组化法和Western blot法测定DRG Nav1.7蛋白的表达水平，采用RT-PCR法测定Nav1.7mRNA的表达水平。结果与C组比较，DNP组和E组MWT和NCV明显下降，DRGNav1.7mRNA及其蛋白表达上调（P〈0．05），S组上述指标差异无统计学意义（P〉0．05）；与DNP组比较，E组MWT升高（P〈0．05），NCV、DRGNav1.7RNA及其蛋白表达水平差异无统计学意义（P〉0．05）。结论DRGNav1.7参与了大鼠糖尿病神经病理性痛的维持。Objective To investigate the role of Nav1.7 in dorsal root ganglia （DRG） in a rat model of diabetic neuropathic pain （DNP）.Methods Thirty-two female Wistar rats aged 3 months weighing 180-220 g were randomly divided into 4 groups （n = 8 each）： control group （group C）, sham operation group （group S）, DNP group and ProTx- I1 （a selective Nav1.7 blocker） group （group E）. Diabetes mellitus was induced by intraperitoneal streptozocin 65 mg/kg. Blood glucose level and mechanical paw withdrawal threshold （MWT）to von Frey filament stimulation were measured 2 weeks later. DNP was confirmed by blood glucose level ≥ 16.0 mmol/L and MWT decreased by more than 50% of the baseline value. Intrathecal catheter was implanted at L5-6 interspace on day 10 after successful induction of DNP. On day 4 after placement of the intrathecal catheter, ProTx- Ⅱ 10 μg/kg was injected intrathecally in group E, while the equal volume of normal saline was given in groups DNP and S. MWT and never conduction velocity （NCV） were measured 1 h after intrathecal injection. The rats were then sacrificed and DRGs of the lumbar segment （L4.6） were removed for determination of Nav1.7 protein expression （by immuno-histochemistry and Western blot） and Nav1.7 mRNA expression （by RT-PCR）.Results The MWT and NCV were significantly lower and the Nav1.7 mRNA and protein expression was significantly higher in groups DNP and E than in group C. ProTx- 11 significantly attenuated the diabetes-induced changes in MWT, but had no effect on NCV and Nav1.7 mRNA and protein expression. Conclusion Nav1.7 in DRG is involved in the maintenance of DNP in rats.

关 键 词：钠通道 糖尿病 神经痛 神经节 脊 

分 类 号：R587.2[医药卫生—内分泌]