鞘内注射ZD7288对糖尿病大鼠周围神经痛及血糖的作用

Effects of ZD7288 on peripheral neuralgia and blood glucose in diabetic rats

目的观察鞘内注射超极化激活环核苷酸门控通道(HCN通道)拮抗剂ZD7288对STZ诱导的Ⅰ型糖尿病大鼠的热痛阈及血糖的影响,探讨背根节HCN通道在糖尿病周围神经痛(DPN)中的作用。方法4~5周龄雄性SD大鼠随机分为3组:对照组、STZ组(鞘内给予生理盐水)和ZD7288+STZ组(鞘内给予ZD7288)。单次腹腔注射链脲佐菌素(STZ,60 mg/kg)制备Ⅰ型糖尿病大鼠模型,分别于注射STZ前1d及注射后7、14、21、28d测定空腹血糖、热缩足反射潜伏期(TWL),免疫印迹技术检测背根节HCN1,2通道的表达。结果与对照组相比,大鼠腹腔注射STZ 2周后空腹血糖显著升高,TWL降低,背根节HCN1,2通道表达显著增高(P<0.01);鞘内给予ZD7288可显著延长糖尿病大鼠TWL,降低背根节HCN1,2表达(P<0.01),但对空腹血糖无显著影响。结论背根节HCN通道表达增加可能促进了糖尿病周围神经痛的发生,鞘内给予HCN通道拮抗剂具有良好的镇痛效应,但对血糖无明显改善作用。

Objective To explore the role of hyperpolarization-activated cyclic nucleotide-gated(HCN)channels in dorsal root ganglionin diabetic neuropathic pain and the effects of HCN channel antagonist ZD7288 on peripheral neuralgia and blood glucose in diabetic rats.Methods Healthy male SD rats(4-5 weeks old)were divided into 3 groups:(1)control group,(2)Streptozotocin(STZ)group(intrathecal administration of saline),(3)ZD7288+STZ group(intrathecal administration of 30g ZD7288).Type I diabetes model was prepared by single intraperitoneal administration of STZ(60 mg/kg).Thermal withdrawal latency(TWL)and fasting blood glucose(FBG)were measured at 1 d before STZ injection and 7,14,21,28 d after STZ injection.The expression of HCN 1,2 channels in dorsal root ganglion was detected by western blot assay.Results Compared with the control group,HCN1,2 channels expression and FBG were increased in diabetic rats.TWL was reduced in diabetic rats.ZD7288 markedly suppressed the increase of HCN1,2 channels expression and the decrease in TWL after STZ injection,but had no significant effect on FBG.Conclusion This study indicates that the increased expression of HCN1,2 channels in dorsal root ganglion may facilitate the pathogenesis of diabetes peripheral neuralgia.HCN channels antagonist has good analgesic effects.