重比重因素对利多卡因诱发糖尿病神经痛大鼠脊髓神经元凋亡的影响

Effect of hyperbaric factor on lidocaine-induced apoptosis in spinal neurons in rats with diabetic neuropathic pain

目的 评价重比重因素对糖尿病神经痛大鼠脊髓神经元凋亡的影响.方法 健康雄性SD大鼠,体重220 ～ 300 g,以高糖高脂饮食＋腹腔注射1％链脲佐菌素（STZ）30 mg/kg制备大鼠糖尿病神经痛模型,注射STZ后3d血糖＞16.65 mmol/L为模型制备成功,随后行鞘内置管.取鞘内置管成功的糖尿病神经痛大鼠24只,采用随机数字表法分为3组（n=8）：重比重利多卡因组（HL组）、等比重利多卡因组（IL组）和葡萄糖组（G组）.另取鞘内置管成功的正常大鼠8只作为对照组（C组）.C组和HL组鞘内注射重比重2％利多卡因10 μl,IL组注射等比重2％利多卡因10 μl,G组注射10％葡萄糖10 μl,1次/d,连续3d.分别记录每次给药后2 min运动阻滞持续时间;于注射STZ前（T1）、鞘内注射前（T2）、第1、2和3天给药后30 min及结束给药后5 d（T3-6）时测定右后爪机械缩足反应阈（PWT）;T时处死大鼠,取L4,5脊髓组织,HE染色,光镜下观察病理学结果;采用TUNEL法检测脊髓神经元凋亡情况.结果 与T1时比较,HL组、IL组和G组T2-5时PWT降低（P＜0.05）;与T2-s时比较,HL组T6时PWT升高（P＜0.05）.与C组比较,HL组运动阻滞持续时间延长,脊髓神经元凋亡指数升高（P＜0.05）;与IL组比较,HL组运动阻滞持续时间延长,脊髓神经元凋亡指数升高（P＜0.05）.结论 重比重因素可促进利多卡因诱发糖尿病神经痛大鼠脊髓神经元凋亡.

Objective To evaluate the effect of hyperbaric factor on lidocaine-induced apoptosis in spinal neurons in rats with diabetic neuropathic pain.Methods Healthy male Sprague-Dawley rats,weighing 220-300 g,were used in the study.Diabetic neuropathic pain was induced by high-sugar high-fat diet ＋ intraperitoneal 1% streptozotocin （STZ） 30 mg/kg and confirmed by blood glucose level 〉 16.65 mmol/L at 3 days after STZ injection and then intrathecal catheter was placed.Twenty-four rats with diabetic neuropathic pain in which IT catheters were successfully implanted were randomly divided into 3 groups （n =8 each）：hyperbaric lidocaine group （group HL）,isobaric lidocaine group （group IL）,and glucose group （group G）.Another 8 rats in which IT catheters were successfully inserted served as control group （group C）.2% hyperbaric lidocaine 10 μl （in C and HL groups）,2% isobaric lidocaine 10 μl （in group IL）,or 10% glucose 10 μl （in group G） was injected intrathecally once a day for 3 consecutive days.The duration of motor block was recorded at 2 min after each administration.The paw withdrawal threshold to von Frey filament stimulation （PWT） was measured before STZ injection （T1）,before IT injection （T2）,at 30 min after administration on 1st,2nd and 3rd days and on day 5 after the end of administration （T3-6）.All the rats were sacrificed at T6 and their L4,5 segments of the spinal cord were removed for microscopic examination.The apoptosis in spinal neurons was detected using TUNEL assay.Results Compared with the baseline value at T1,PWT was significantly decreased at T2-5 in HL,IL and G groups.PWT was significantly higher at T6 than at T2-5 in group HL.Compared with group C,the duration of motor block was significantly prolonged and the apoptotic index was increased in group HL.Compared with group IL,the duration of motor block was significantly prolonged and the apoptotic index was increased in group HL.Conclusion Hyperbaric factor can promote lidocaine-induced apoptosis in spinal neurons in rats with diabetic neuropathic pain.