腹腔注射右美托咪定对糖尿病神经病理性疼痛大鼠脊髓胶质细胞活化的影响

目的 探讨腹腔注射右美托咪定(dexmedetomidine,Dex)对糖尿病神经病理性疼痛(diabetic neuropathic pain,DNP)大鼠脊髓胶质细胞活化及炎症因子表达的影响. 方法 健康清洁级雄性SD大鼠32只,体重180～200 g,采用随机数字表法大鼠分为4组(每组8只):对照组(C组)、DNP组、Dex组和α2受体拮抗剂组(YOH组).采用链脲佐菌素(streptozotocin,STZ)注射法建立大鼠DNP模型.从STZ注射28 d开始:Dex组连续7d腹腔注射Dex 50 μg/kg;YOH组连续7d腹腔注射育亨宾0.1 mg/kg,之后30 min腹腔注射Dex 50 μg/kg.于注射STZ后29～35 d测定各组大鼠机械缩足反射阈值(mechanical withdrawal threshold,MWT).于35 d测定MWT后处死大鼠,采用免疫荧光双标法测定各组大鼠脊髓内小胶质细胞和星形胶质细胞的活化情况,采用ELISA法检测各组大鼠脊髓内TNF-α和IL-1的含量. 结果 与C组比较,DNP组、Dex组、YOH组3组大鼠均体重下降、血糖升高(P＜0.05);DNP组、Dex组和YOH组3组大鼠组间比较,体重和血糖差异无统计学意义(P＞0.05).与C组比较,DNP组和YOH组术后各时点MWT均降低(P＜0.05);与DNP组比较,Dex组术后各时点MWT均升高(P＜0.05).与C组比较,DNP组和YOH组大鼠脊髓内小胶质细胞活化率、TNF-α和IL-1的含量均升高(P＜0.05);与DNP组比较,Dex组大鼠脊髓内小胶质细胞活化率、TNF-α和IL-1的含量均降低(P＜0.05);各组大鼠组间比较,脊髓内星形胶质细胞活化率差异无统计学意义(P＞0.05). 结论 Dex能够缓解DNP大鼠的痛觉过敏,其机制可能与抑制小胶质细胞活化,从而减轻脊髓内炎症反应有关.

Influences of intraperitoneal injection of dexmedetomidine on activation of spinal glial cells in diabetic neuropathic pain rats

Objective Exploring the influences of intraperitoneal injection of dexmedetomidine (Dex) on activation of spinal glial cells and expression of inflammatory factors in rats with diabetic neuropathic pain(DNP).Methods Thirty two health male SD rats,weight 180-200 g,were divided into four groups (n=8) according the random number table method.The four groups included the control group (group C),diabetic neuropathic pain group (group DNP),group Dex and oα2 receptor antagonist group (group YOH).Streptozotocin (STZ) was used to establish the DNP model in rats.Starting from 28 d after STZ injection,Dex group was given intraperitoneal injection of Dex (50 μg/kg) for consecutive 7 d,while group YOH was given intraperitoneal injection of Yohimbine (0.1 mg/kg) 30 min before intraperitoneal injection of Dex(50 μg/kg) for consecutive 7 d.Mechanical withdrawal threshold (MWT) was determined in each group of rats 29-35 d after STZ injection.Rats were sacrificed after MWT detection on 35 d.Immunofluorescence double-staining was used to detect activation of microglia and astrocytes in rat spinal cord of each group.ELISA was used to measure TNF-α and IL-1 expression in rat spinal cord of each group.Results Compared with group C,rat body weights were decreased while blood glucose values were increased in group DNP,group Dex and group YOH (P＜0.05).But there were no statistically significant differences among group DNP,Dex and YOH in rat body weights and blood glucose levels (P＞0.05).Compared with group C,MWT at all time points decreased in group DNP and group YOH(P＜0.05).Compared with group DNP,MWT at all time points after operation increased in group Dex (P＜0.05).Compared with group C,activation rates of microglia and expression of TNF-α and IL-1 were all increased in rat spinal cords of group DNP and group YOH(P＜0.05).Compared with group DNP,activation rates of microglia and expression levels of TNF-α and IL-1 were all decreased in rat spinal cord of group Dex (P＜0.05).There were no statistically significant differences among groups in activation rates of spinal astrocytes (P＞0.05).Conclusions Dex can relieve hyperalgesia in rats with diabetic neuropathy pain.The underlying mechanism may be related to inhibition of microglia activation and reduction of the inflammatory reaction in spinal cord.