N-乙酰半胱氨酸对大鼠急性脊髓损伤后继发性脊髓损伤的保护作用

Protective effect of N-acetylcysteine on the secondary spinal injury in rats after acute spinal cord injury

目的探讨N-乙酰半胱氨酸(NAC)对大鼠脊髓急性损伤后继发性脊髓损伤的保护机制。方法成年SD大鼠18只随机均分成单纯椎板切除(对照组)、急性脊髓损伤(损伤组)和急性脊髓损伤后NAC治疗(治疗组)三组。用30g力量动脉瘤夹从两侧夹闭脊髓30s建立脊髓损伤模型。治疗组术后15min、1、2和3d分别予NAC 150mg/kg腹腔注射;对照组和损伤组腹腔注射等量生理盐水。所有动物于术后3d处死取材,用凝胶电泳迁移率分析和免疫组化检测脊髓组织中核因子κB(NF-κB),ELISA法检测肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)和IL-6表达。结果损伤组脊髓组织中NF-κB、TNF-α、IL-1β和IL-6水平均比对照组升高(P<0.05),治疗组脊髓组织中各因子水平均比损伤组显著降低(P<0.05)。结论 NAC可以通过抑制大鼠急性脊髓损伤后NF-κB的活性,进一步下调TNF-α、IL-1β和IL-6的表达,从而减轻继发性炎症反应所导致的脊髓损伤。

Objective To investigate the underlying mechanism for N-αcetylcysteine（NAC） to reduce the secondary spinal cord injury in rats underwent acute spinal cord injury（ASCI）. Methods ASCI models were established by clipping the spinal cord using 30 g force aneurysm clip for 30 s. Eighteen SD rats were equally randomized into three groups. The rats in group J were taken as ASCI model controls and those in group T were treated with intraperitoneal injection of NAC 150 mg/kg at 15 min,on the 1st ,2nd ,and 3rd day after ASCI. The rats in group L underwent laminectomy alone,but without spinal injury. All rats were sacrificed on the 3^nd day after ASCI and the spinal cord was taken out for detecting the expressions of nuclear factor-kappa B（NF-κB） with EMSA and immunohistoche- mistry, tumor necrosis factor-α （TNF-α）, interleukin-1β （IL-1β） and IL-6 with ELISA. Results The expressions of NF-κB,TNF-α, IL-1β and IL-6 were higher in group J than those in group L, which were lower in group T than those in group J（P〈0. 05）. Conclusion NAC may reduce the secondary spinal cord iniury in rats underwent ASCI hy inhibiting the activation of NF-κB after ASCI and further downregulating the levels of inflammatory cytokines such as TNF-α, IL-1β and IL-6.