免疫抑制剂可能通过抑制中枢小胶质细胞活化提高CCI大鼠热耐受时间

Immune Suppression Might Attenuate Thermal Hyperalgesia Via Inhibition the Activity of Microglials in Chronic Constriction Injury of the Sciatic Nerve Rat Models

目的观察外周神经损伤后，在免疫抑制剂对热痛觉过敏改善的情况下，免疫抑制剂是否通过影响中枢神经系统小胶质细胞的活化提高慢性坐骨神经缩窄损伤（chronic constriction injury of the sciatic nerve，CCI）模型大鼠的热耐受时间。方法通过结扎大鼠坐骨神经建立CCI模型。将雄性SD大鼠20只随机分为环孢素（CsA）组和生理盐水组。造模术后第3天神经性疼痛表现明显后，CsA组按体重6mg／kg（浓度10mg／mL）经腹腔注射CsA，NS组经腹腔注射等体积生理盐水。2周时处死大鼠取腰段脊髓并制成切片，用免疫组化方法观察中枢小胶质细胞在疼痛刺激下的形态和分布变化以及免疫抑制剂的影响。结果CsA组注射CsA后热痛觉过敏明显减轻，10d后热耐受时间恢复至造模术前水平。生理盐水组在脊髓L4～6节段的灰、白质中均可见大量活化的小胶质细胞，而CsA组在相应部位均可见正常形态的小胶质细胞，CsA组腰段脊髓灰质、白质内小胶质细胞的平均吸光度值均明显低于NS组（P〈0．05）。结论免疫抑制剂CsA可抑制中枢小胶质细胞的活化，并与神经损伤后的热痛觉过敏的改善有关。

Objective To observe the change of morphology and distribution of microglia cells following the treatment of cyclosporin A （CsA） in the established neuropathic pain in chronic constriction injury of the sciatic nerve （CCI） rat model. Methods The CCI was carried out in 20 SD rats. All rats were randomly accepted CsA （6 mg/kg i. p. ） or same volume of saline every day since the 3rd day until the 14th day postoperatively. The thermal latencies and mechanical thresholds of each rats were measured preoperatively and on the 3rd, 4th, 6th, 8th, 10th and 14th post-operative day. Rats were sacrificed on the 14th day and the L4-6 sections of lumbar spinal cords of all rats were harvested for immunohistochemical examination of microglials. Results When CsA / was injected on the 3rd day after nerve injury, the reduced thermal latencies went up significantly after the treatment and gradually recovered in 10 days. In the CsA treatment group,a few number of microglia cells with normal morphology distributed in the white matter and the grey matter of the spinal cord L4-6. In the NS treatment group, a great number of microglia cells were scatterd in the white matter and the grey matter of the spinal cord L4-6. The mean optical density of of L4-6 sections of spinal cord in both white matter and grey matter significantly decreased in the CsA treatment group compared with that in the NS treatment, group （P〈0.05）. Conclusions Immune suppression reagent CsA inhibited the activity of microglia cells in the CNS. The present work might reveal the mechanisms of neuropathic pain attenuation of immune suppression followed by chronic nerve injury.