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目的:探讨硒代胱氨酸(SeC)对小鼠短暂局灶性脑缺血再灌注(transient focal cerebral ischemia/reperfusion，tFCI/R)损伤的神经保护作用及机制。方法:线栓阻塞昆明小鼠大脑中动脉1 h后拔除，制作tFCI/R模型。通过多普勒血流监测和神经功能缺损评分筛选手术合格小鼠40只，按照随机数字表法分为SeC治疗组和tFCI/R模型对照组；另选20只作为假手术组(Sham组，小鼠经历手术全程而不阻塞大脑中动脉)。SeC治疗组小鼠给予术后0 h、24 h、48 h各1次腹腔注射SeC溶液(2 mg/30 g)；模型组和Sham组小鼠给予同样方式注射等量生理盐水。于术后24 h、48 h、72 h每组各随机抽取6只小鼠进行神经功能缺损评分及神经行为学测试；之后所有小鼠麻醉处死取脑，行氯代三苯基四氮唑(TTC)染色测脑梗死体积，湿-干重法测脑水肿程度变化，Tunel-DAPI染色观察神经元凋亡情况，Western blot检测活性caspase-3和PARP表达，并检测小鼠脑组织GSH、GSH-Px表达情况。结果:Sham组小鼠未见神经功能缺损表现，术后24 h、48 h、72 h的tFCI/R组Zea Longa评分[(3.67±0.52)分，(3.33±0.52)分，(2.17±0.41)分]均比Sham组[(0.50±0.55)分，(0.67±0.52)分，(0.33±0.52)分]显著提高(n t＝10.26，8.86，6.81，均n P<0.05)，而SeC治疗组评分[(2.50±0.55)分，(1.67±0.82)分，(0.83±0.75)分]则比tFCI/R组显著降低(n t＝3.74，4.19，3.84，均n P<0.05)。行为学评测结果与Zea Longa评分一致。术后72 h TTC染色显示：与tFCI/R组[(24.69±2.25)%]比较，SeC治疗组[(11.89±1.64)%]脑梗死体积明显缩小，差异有统计学意义(n t＝10.28，n P<0.05)；Sham组无梗死灶形成。湿-干重测量显示：与Sham组相比，tFCI/R组左侧脑组织含水量[(85.87±1.36)%]明显增加(n t＝8.73，n P<0.05)，SeC治疗组左侧脑组织含水量[(81.06±1.07)%]与tFCI/R组比较下降，差异有统计学意义(n t＝6.22，n P<0.05)。Tunel-DAPI染色、Western blot结果表明，SeC处理显著下调了caspase-3和PARP的裂解，从而抑制了神经元凋亡。脑组织GSH含量检测证实，与tFCI/R组[(64.69±2.15)%]比较，SeC治疗组GSH含量[(85.83±1.46)%]显著提高，差异有统计学意义(n t＝18.19，n P<0.05)。脑组织GSH-Px活性检测证实，与tFCI/R组[(38.74±1.93)%]比较，SeC治疗组GSH-Px活性[(49.12±1.13)%]显著提高，差异有统计学意义(n t＝10.38，n P<0.05)。n 结论:SeC通过抑制氧化应激和凋亡，对tFCI/R诱导的脑损伤发挥了有效的神经保护作用，据此推测SeC在脑卒中的防治方面具有潜在的应用价值。“,”Objective:To investigate the neuroprotective effect and mechanism of selenocysteine(SeC) on transient focal cerebral ischemia/reperfusion(tFCI/R) injury in mice.Methods:A tFCI/R model was established in Kunming mice after 1 hour of middle cerebral artery occlusion. Forty mice qualified for surgery were screened by doppler blood flow monitoring and neurological function defect score, and were randomly assigned to the SeC treatment group and the tFCI/R control group, while another 20 mice were selected as the Sham operation control group (underwent the whole operation without middle cerebral artery obstruction). Mice in SeC treatment group were given SeC solution intraperitoneal injection (2 mg/30 g) once at 0 h, 24 h and 48 h after surgery, and mice in the tFCI/R group and Sham group were injected with the same amount of saline in the same manner. At 24 h, 48 h and 72 h after surgery, 6 mice were randomly selected from each group for neurological impairment score and neurobehavioral test. Then the volume of cerebral infarction was measured by TTC staining, the degree of cerebral edema was measured by wet-dry weight method, the apoptosis of neurons was observed by Tunel-DAPI staining, the activity of caspase-3 and PARP were detected by Western blot, and the expressions of GSH and GSH-PX in mouse brain tissues were detected.Results:The Zea Longa scores of tFCI/R group((3.67±0.52), (3.33±0.52), (2.17±0.41) points) at 24h, 48h and 72h after surgery were significantly higher than that of Sham group((0.50±0.55), (0.67±0.52), (0.33±0.52)) (n t=10.26, 8.86, 6.81, all n P<0.05). The scores of SeC treatment group ((2.50±0.55), (1.67±0.82), (0.83±0.75)) were significantly lower than that of tFCI/R group (n t=3.79, 4.19, 3.84, all n P<0.05). The behavioral assessment results were consistent with the Zea Longa score. TTC experiment 72 h after surgery showed that no infarction lesion was formed in Sham group. Compared with tFCI/R group ((24.69±2.25)%), SeC treatment group ((11.89±1.64)%) had significantly reduced cerebral infarction volume, and the difference was statistically significant (n t=10.28, n P<0.05). Wet-dry weight measurement showed that compared with Sham group, the moisture content ((85.87±1.36)%) of left brain tissue in tFCI/R group increased significantly (n t=8.73, n P<0.05), the water content of left brain tissue in SeC treatment group ((81.06±1.07)%) decreased compared with tFCI/R group, and the difference was statistically significant (n t=6.22, n P<0.05). Tunel-DAPI staining and Western blot results showed that SeC treatment significantly down-regulated the cleavage of caspase-3 and PARP, thus inhibiting neuronal apoptosis. GSH content in brain tissue was significantly increased in SeC treatment group ((85.83±1.46)%) compared with tFCI/R group ((64.69±2.15)%), and the difference was statistically significant (n t=18.19, n P<0.05). The activity of GSH-PX in brain tissue was significantly increased in the SeC treatment group ((49.12±1.13)%)compared with the tFCI/R group ((38.74±1.93)%), and the difference was statistically significant (n t=10.38, n P<0.05).n Conclusion:SeC plays an effective neuroprotective role in tFCI/R-induced brain injury by inhibiting oxidative stress and apoptosis, which confirms the potential application value of SeC in the prevention and treatment of stroke.