甘氨酸通过抑制大鼠创伤性脑损伤后炎症反应来发挥神经保护作用

The glycine protects against traumatic brain injury in rats through suppressing the release of pro-inflammatory cytokines

目的探讨甘氨酸对创伤性脑损伤(TBI)大鼠的神经保护作用及机制。方法将SD雄性大鼠随机分为对照(Sham)组、脑损伤+溶剂(TBI+Vehicle)组和脑损伤+甘氨酸(TBI+Glycine)组,采用Feeney's自由落体法建立创伤性脑损伤模型;术后1 h侧脑室注射甘氨酸(2 mg/kg)或等体积的溶剂;术后24 h,取脑组织样本;采用脑含水量测定、蛋白免疫印迹法和免疫荧光法评价甘氨酸对大鼠TBI的神经保护作用;采用ELISA法检测炎症因子白介素1β(IL-1β)、白介素6(IL-6)和肿瘤坏死因子α(TNF-α)的表达水平,评价甘氨酸对TBI后脑组织炎症反应的抑制作用。结果甘氨酸可减轻TBI后脑水肿,减少皮层神经元损伤;同时甘氨酸可抑制TBI后炎症因子IL-1β、IL-6和TNF-α的过度释放。结论甘氨酸对大鼠TBI具有神经保护作用;甘氨酸对TBI后相关炎症因子过度增高的抑制可能部分解释其神经保护作用机制。

Objective To investigate the neuroprotective effects of the glycine on traumatic brain injury （TBI） in rats and its mechanism. Methods Male SD rats were randomly divided into sham group, TBI ＋ Vehicle group, TBI ＋ Glycine group. Experimental TBI was nduced using Feeney＇s weigh-drop method. Glycine （2 mg/kg） or vehicle was treated through intracerebroventricular injection at i h post-injury. Brain samples were taken from the sacrificed rats at 24 h after TBI. Brain water content, Western blot and Irnmuno- fluorescence were used to investigate the neuroprotection of Glycine against TBI. ELISA was performed to e- valuate the expression levels of inflammatory cytokines including interleukin-1β （IL-1β）, interleukin-6 （IL-6） and tumor necrosis factor α （TNF-α） to confirm the anti-inflammatory activity of glycine. Results The glycine significantly alleviated brain edema, and reduced the cortical neuron damage. In addition, glycine could inhibit the excessive release of inflammatory cytokine including IL-1β, IL-6 and TNF-α after TBI. Conclusion This study indicated that the glycine confered neuroprotection on TBI in rats, and suggested that the neuroprotec- tive effect of the glycine might be mediated partially through its suppression of pro-inflammatory cytokine re- lease.