米诺环素对神经病理性疼痛大鼠海马促炎性细胞因子表达的影响

Effect of Minocycline on the Expression of Pro-inflammatory Cytokines in Hippocampus of Rats with Neuropathic Pain

目的观察米诺环素对腰5脊神经横断(L5-SNT)所致神经病理性疼痛大鼠模型海马水平TNF-α、IL-1β、IL-6表达变化的影响。方法将雄性SD大鼠36只完全随机法分成4组,即正常组(Z组)、假手术组(J组)、模型+生理盐水组(MS组)及模型+米诺环素组(MM组),每组9只。MS组、MM组进行SNT神经病理性疼痛大鼠模型建立,而后MM组每天给予米诺环素40mg/kg腹腔内注射,而MS组给予同等剂量的生理盐水腹腔内注射。术后观察各组大鼠行为学变化并于术前1天及术后1~11天测定大鼠机械缩足阈值(PWT);选择术后第2、7、11天随机取每组动物处死,应用实时PCR法检测大鼠海马水平TNF-α、IL-1β及IL-6的表达。结果(1)行为学检测:与术前1天比较,MS组与MM组大鼠出现明显的机械性痛觉过敏(P<0.05),而与MS组比较,MM组大鼠机械性痛觉过敏得到明显改善(P<0.05)。(2)促炎性细胞因子变化:与J组比较,MS组大鼠海马TNF-α、IL-1β、IL-6表达上调(P<0.05),而与MS组比较,MM组大鼠海马TNF-α、IL-1β、IL-6的表达均有不同程度的下降(P<0.05)。结论米诺环素具有明显的镇痛作用,其作用机制可能与抑制海马中TNF-α、IL-1β及IL-6的表达及释放有关。

Objective To analyze the effect of minocycline on the expression of TNF-α,IL-1β and IL-6 in the hippocampus of rats suffered from neuropathic pain,which was induced by L5 spinal nerve transection (L5-SNT).Methods Thirty-six male Sprague-Dawley rats were randomly divided into 4 groups:normal group (Z group),sham operation group (J group),model + saline group (MS group) and model + minocycline group (MM group)( n =9 each group).The SNT neuropathic pain rat model was established in MS and MM group.MM group was injected intraperitoneally with minocycline (40mg/kg) every day after SNT neuropathic pain model was established,while MS group was given with the same dose of saline.The behavior changes of rats were observed and the paw withdrawl threshold (PWT) were measured at one day before and one^eleven day after SNT operation.Rats were killed and hippocampus were removed at two,seven,eleven days after operation and the expression of TNF-α,IL-1β and IL-6 in hippocampus were detected by RT- PCR.Results (1)Results of behavioral tests:compared with one day before operation,the rats in the MS group and the MM group showed obvious mechanical hyperalgesia ( P <0.05),However,compared with the MS group,mechanical hyperalgesia was significantly improved in rats of MM group( P <0.05).(2) Changes of pro-inflammatory cytokine:compared with J group,the expression of TNF-α,IL-1β,IL-6 in hippocampus of MS group was up-regulated ( P <0.05).When compared with MS group,the expression of TNF-α,IL-1β,IL-6 in hippocampus of MM group was down-regulated to some extent ( P <0.05).Conclusion Minocycline has obvious analgesic effect,which may be related to inhibiting the expression and release of TNF-α,IL-1β and IL-6 in hippocampus.