Wang Guo-hua, Jiang Zheng-lin, Zhang Xiang-gen, Shen Li-hua, Fan Xing-juan
Institute of Nautical Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2010 Feb;26(1):72-6.
To observe the therapeutic time window of L-serine against focal cerebral ischemia/reperfusion injury in rats, and related mechanisms.
Sprague-Dawley rats were randomly divided into six groups (n=6), sham-operation group, vehicle group, 3, 6, 12 and 24 h treatment group of L-serine. Focal cerebral ischemia was induced with the method of middle cerebral artery occlusion (MCAO) in rats, and reperfusion was emerged by removing the thread 2 h later. The treatment of L-serine (200 mg/kg ip) was begun at 3, 6, 12 and 24 h after MCAO respectively, and subsequently repeated once 12 h. The vehicle group was intraperitoneally injected with isodose normal saline. The neurological behavior score and cerebral infarction volume was measured 48 h after reperfusion. In addition, the contents of malondialdehyde (MDA), activity of superoxide dismetase (SOD), the levels of inflammatory cytokines (TNF-alpha, IL-6) and ultrastructure of neuron in brain tissue were investigated.
Compared with the vehicle group, treatments with L-serine both 3 and 6 h after MCAO decreased the neurology deficit score and infarct volume. Only neurology deficit score had been reduced 12 h after MCAO, while no neuropmrotective effects had been observed during 24 h. Furthermore, L-serine elevated the content of SOD, decreased the level of MDA, TNF-alpha and IL-6 in ischemic brain tissue, and alleviated the injury of the neuronal ultrastructure.
L-serine exerted a time-dependent neuroprotective effect on the brain after MCAO in rat. This effect might be possibly mediated through following mechanisms: lessening oxidative stress and reducing the release of inflammatory cytokines.
观察L-丝氨酸对大鼠局灶性脑缺血/再灌注损伤的治疗时间窗及相关机制。
将Sprague-Dawley大鼠随机分为六组（n = 6），即假手术组、溶剂对照组、L-丝氨酸3、6、12和24小时治疗组。采用大脑中动脉闭塞（MCAO）法诱导大鼠局灶性脑缺血，2小时后抽出栓线实现再灌注。分别于MCAO后3、6、12和24小时开始给予L-丝氨酸（200 mg/kg腹腔注射）治疗，随后每12小时重复给药一次。溶剂对照组腹腔注射等剂量生理盐水。再灌注48小时后测量神经行为评分和脑梗死体积。此外，检测脑组织中丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性、炎性细胞因子（TNF-α、IL-6）水平及神经元超微结构。
与溶剂对照组相比，MCAO后3和6小时给予L-丝氨酸治疗可降低神经功能缺损评分和梗死体积。MCAO后12小时仅神经功能缺损评分有所降低，而24小时内未观察到神经保护作用。此外，L-丝氨酸可提高缺血脑组织中SOD含量，降低MDA、TNF-α和IL-6水平，并减轻神经元超微结构损伤。
L-丝氨酸对大鼠MCAO后脑组织具有时间依赖性神经保护作用。这种作用可能通过减轻氧化应激和减少炎性细胞因子释放等机制介导。
