硫化氢后处理对短暂性全脑缺血模型保护作用的研究

发布时间：2018-11-13 16:40

【摘要】：目的:明确硫化氢后处理在短暂性群脑缺血模型中的最佳后处理时间及最佳后及处理剂量。研究Kv4.2和VEGF在此模型中神经保护机制及他们与硫化氢的关系。方法:选取雄性Wistar大鼠,体重200-280g。采取四血管闭塞方法制作短暂性全脑缺血模型。选择不同的硫化氢后处理时间及不同的硫化氢后处理剂量。用Nissl染色计数大鼠海马CA1区细胞数,判断最佳的后处理时间及剂量。采用Western blot观察不同组别间Kv4.2和VEGF的表达变化。结果:(1)硫化氢后处理可以对短暂性全脑缺血15min后大鼠海马CA1区神经元起到保护作用;(2)其保护作用给药时间窗为缺血后12-48小时;(3)保护剂量与给药时间有关;(4)在缺血后12小时给药,24umol组和48umol组较缺血再灌注组比均有明显保护作用(P0.05),且48umol组比24umol组保护作用更明显(P0.05);(5)在缺血后24小时给药,24umol组和48umol组较缺血再灌注组比均有明显保护作用(P0.05),但两组间保护作用无明显差异(P0.05);(6)在缺血后48小时给药;仅24umol组具有保护作用(P0.05);(7)在给予24umol/kg的硫化氢后处理时,不同的后处理时间神经元保护作用的强弱不同,24umol/kg的剂量在缺血再灌注后24小时给药保护作用最强(P0.05);(8)在给予48umol/kg的硫化氢后处理时,也在缺血再灌注24小时给药保护作用最强(P0.05);(9)144umol组在缺血再灌注12小时、24小时、48小时分别给药给药均未发现保护作用;(10)Kv4.2在缺血38小时后表达量较假手术组降低(P0.05),但给予硫化氢组较单纯缺血组表达量增高(P0.05),但并未超过假手术组(P0.05);(11)VEGF在缺血后较假手术组表达量明显上升(P0.05),给予硫化氢组较单纯缺血组升高更明显(P0.05)。结论:(1)在短暂性全脑缺后12-48小时给予小计量硫化氢后处理可以起到神经元保护作用,相同计量在不同时间给药保护效果不同;(2)硫化氢后处理可能通过抑制Kv4.2下降及上调VEGF达到神经保护作用。
[Abstract]:Aim: to determine the optimal post-treatment time and dose of hydrogen sulfide post-treatment in transient swarm cerebral ischemia model. To study the neuroprotective mechanism of Kv4.2 and VEGF in this model and their relationship with hydrogen sulfide. Methods: male Wistar rats were selected. The model of transient global ischemia was established by four-vessel occlusion. Choose different hydrogen sulfide after treatment time and different hydrogen sulfide after treatment dose. The number of CA1 cells in hippocampus of rats was counted by Nissl staining to determine the optimal post-processing time and dose. Western blot was used to observe the expression of Kv4.2 and VEGF in different groups. Results: (1) hydrogen sulfide post-treatment could protect hippocampal CA1 neurons after transient global cerebral ischemia (15min), (2) the protective effect was 12-48 hours after ischemia. (3) the protective dose was related to the administration time, (4) 12 hours after ischemia, the protective effects of 24umol group and 48umol group were significantly higher than that of ischemia-reperfusion group (P0.05), and the protective effect of 48umol group was more obvious than that of 24umol group (P0.05). (5) after 24 hours of ischemia, 24umol group and 48umol group had significant protective effects (P0.05), but there was no significant difference between the two groups (P0.05); (6) 48 hours after ischemia. Only 24umol group had protective effect (P0.05). (7) when 24umol/kg was treated with hydrogen sulfide, the protective effect of neuron was different in different postprocessing time, and the dose of 24umol/kg was the strongest at 24 hours after ischemia reperfusion (P0.05); (8) when 48umol/kg was treated with hydrogen sulfide, the protective effect was the strongest at 24 hours after ischemia reperfusion (P0.05). (9) there was no protective effect in 144umol group after 12 hours, 24 hours and 48 hours of reperfusion. (10) after 38 hours of ischemia, the expression of Kv4.2 was lower than that of sham-operation group (P0.05), but the expression of Kv4.2 in hydrogen sulfide group was higher than that in ischemic group (P0.05), but not higher than that in sham-operation group (P0.05). (11) the expression of VEGF in ischemic group was significantly higher than that in sham-operated group (P0.05), and that in hydrogen sulfide group was higher than that in ischemic group (P0.05). Conclusion: (1) treatment with small dose of hydrogen sulfide at 12-48 hours after transient global brain deficiency can protect neurons, and the same dose has different protective effects at different time. (2) after treatment with hydrogen sulfide, the neuroprotective effect may be achieved by inhibiting the decrease of Kv4.2 and upregulating VEGF.
【学位授予单位】：青海大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R743.31

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