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作 者:薛莉[1] 李金声[1] 李娅[1] 任杰[1] 谢小萍[1] 常耀明[1] 王文岚[1]
机构地区:[1]第四军医大学航空航天医学系,陕西西安710032
出 处:《现代生物医学进展》2015年第12期2245-2250,2298,共7页Progress in Modern Biomedicine
基 金:国家自然科学基金项目(81101466)
摘 要:目的:通过研究高压氧(HBO)治疗急性CO中毒大鼠海马不同分区神经细胞凋亡情况,探讨HBO治疗急性CO中毒的应用及机理。方法:利用雄性SD大鼠,建立急性CO中毒模型。应用免疫组织化学以及免疫荧光的方法,测定在染毒和CO中毒HBO治疗后1 d、3 d、7 d、14 d和21d Bcl-2、caspase-3、Neu N、BAX和MMP-9的表达水平的变化。结果:海马CA3区神经细胞对急性CO中毒与HBO治疗比CA1和CA2区更加敏感;急性CO中毒后,海马各区神经细胞凋亡程度随1 d、3 d、7 d、14 d和21 d时间延长而加重;BAX、caspase-3和Bcl-2等凋亡相关因子的表达水平与MMP-9的变化趋势一致:在1d开始增多,3d达到最大值,7d开始减少,14 d与21 d与正常组类似;CO中毒大鼠进行HBO治疗后,海马各区MMP-9、BAX、caspase-3和Bcl-2的表达水平明显降低;且HBO治疗7 d后,海马各区这些凋亡相关因子的表达降低最为明显。结论:海马CA3区神经细胞对急性CO中毒及HBO治疗敏感;海马神经细胞凋亡可能与神经细胞表达MMP-9降解神经细胞周围的基质,表达BAX、caspase-3和Bcl-2等凋亡相关因子促进凋亡发生有关;HBO治疗可降低MMP-9以及BAX、caspase-3和Bcl-2等凋亡因子的表达,抑制神经细胞的凋亡;HBO治疗7d对神经细胞凋亡的抑制作用最明显。Objective: To investigate the effects and mechanism of hyperbaric oxygen (HBO) therapy on neuronal apoptosis in different hippocampal areas after acute carbon monoxide (CO) poisoning. Methods: The animal model of acute CO poisoning was established. Then the SD rats were treated with hyperbaric oxygen therapy, lmmunohistochemistry and immunofluorescence were used to determine the expression levels of Bcl-2, caspase-3, NeuN, MMP-9 and BAX at 1 d, 3 d, 7 d, 14d and 21 d. Results: Neurons of CA3 area were more sensitive than those of CA1 and CA2 after acute CO poisoning and HBO therapy; after acute CO poisoning, the apoptosis ofhippocampal neurons was aggravated at ld, 3d, 7d, 14d and 21d with prolonged days. The expressions ofBAX, caspase-3 and Bcl-2 regulating neuronal apoptosis were consistent with the level of MMP-9: it began to increase at 1 d, reached to the maximum at 3d, started to decrease at 7d, and it was similar to the normal control group at 14 d and 21 d; for the CO poisoning rats treated with HBO therapy, the expressions of MMP-9, caspase-3, BAX and Bcl-2 in hippocampus were obviously decreased. On day 7, the inhibitory effect of HBO therapy was the most obvious. Conclusions: Neurons ofhippocampal area CA3 is more sensitive than CA1 and CA2 for the treatment of acute CO poisoning and HBO; the apoptosis may be related with matrix degradation of MMP-9 and the pro-apoptosis function of BAX, caspase-3 and Bcl-2; HBO therapy can reduce the expressions of MMP-9 and BAX, caspase-3 and Bcl-2, then inhibit neuronal apoptosis.
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