代谢型谷氨酸受体在大鼠糖尿病神经病理性疼痛中的作用

Role of mGluR5 in diabetic neuropathic pain in rats

目的评价代谢型谷氨酸受体(mGluR5)在大鼠糖尿病神经病理性疼痛中的作用。方法 3月龄Wistar大鼠,雌雄不限,体重180～220g,单次腹腔注射链脲佐菌素(STZ)65mg/kg制备糖尿病大鼠神经病理性疼痛模型。模型制备成功大鼠64只,随机分为2组(n=32),糖尿病神经病理性疼痛组(D组)和mGluR5拮抗剂组(M组),另取32只正常大鼠作为对照组(C组,n=32)。M组腹腔注射mGluR5拮抗剂20mg/kg,1次/d,C、D组注射等体积生理盐水。各组分别于第2、4、6、8周(T1～4)末随机取8只大鼠,采用vonFrey纤维丝测定双后足机械缩足反应阈值(MWT),取L3～6脊髓,采用免疫组化法和RT-PCR法检测mGluR5的mRNA水平。结果与C组比较,D组T1～4时MWT降低,mGluR5mRNA水平升高(P<0.05);与D组比较,M组T1～4时MWT升高mGluR5mRNA水平下降(P<0.05)。结论 mGluR5激活参与大鼠糖尿病神经病理性疼痛的形成。

Objective To evaluate the role played by mGluR5 in diabetic neuropathic pain （DNP） in rats.Methods 96 Wistar rats 3 months old weighing 180～220 g were randomly divided into 3 groups：groupⅠcontrol （C）;groupⅡ DNP;group Ⅲ MPEP （selective mGluR5 inhibitor） ＋ DNP.Diabetes mellitus （DM） was induced by intraperitoneal streptozocin 65 mg/kg.Blood glucose level was measured every week for 4 weeks.DM was confirmed by blood glucose level ≥16.0 mmol/L in the 4th week.Mechanical paw withdrawal threshold to von Frey filament stimulation （MWT） was measured at the end of the 4th week.Diabetic rats with significant decrease in MWT were used in groupⅡand Ⅲ.Starting from the 5th week after DNP had been induced,MPEP 20 mg/kg were given by intraperitoneal injection once a day in group Ⅲ.Eight animals were taken from each group for MWT measurement at the end of the 2nd,4th,6th and 8th week after the model was successfully made respectively.The rats were then killed and the lumbar segment of the spinal cord were removed for microscopic examination and determination of the level of mGluR5 mRNA.Results The MWT were significantly lower and the mGluR5 mRNA level were significantly higher in groupⅡ,MPEP significantly attenuated the diabetes-induced changes in group Ⅲ.Conclusions mGluR5 is involved in the DNP.