甘露醇、尼莫地平及其两药联合应用对脑缺血大鼠神经保护作用的机制研究

Neuroprotective effects of mannitol,nimodipine and mannitol combined with nimodi pine in the treatment of cerebral ischemia and reperfusion in rats

目的:探讨甘露醇与尼莫地平联合应用治疗大鼠局灶性脑缺血再灌注损伤的作用机制。方法:SD大鼠60只,按随机对照实验设计等分成5组,每组12只。A组:假手术组;B组:模型组,即局灶性脑缺血再灌注组;C组:甘露醇组;D组:尼莫地平组;E组:甘露醇与尼莫地平合用组。采用TUNEL法及TBA法分别观察脑组织凋亡细胞数目及丙二醛含量。结果:①B组缺血侧脑组织凋亡细胞数目(46.6±11.0)个/视野及丙二醛含量(0.75±0.07)μmol/g均明显高于A组假手术侧(t=10.10,15.43,P<0.01)。②C组、D组、E组缺血侧脑组织凋亡细胞数目及丙二醛含量均较B组缺血侧脑组织降低(P<0.05),其中E组脑组织凋亡细胞数目及丙二醛含量降低最显著(P<0.05)。结论:甘露醇、尼莫地平及两药合用均可通过抑制神经细胞凋亡和降低丙二醛含量发挥对局灶性脑缺血再灌注损伤的神经保护作用,其中两药合用效果更佳,为临床两药合用改善缺血性脑血管病患者的神经功能提供了理论依据。

AIM:To study the neuroprotective effects of mannitol combined with nimodipine in the treatment of focal cerebral ischemia and reperfusion in rats. METHODS: Sixty SD rats were randomly divided into five groups of 12 rats eac h: sham operation group(group A),model group or focal ischemia and reperfusion g roup(group B),mannitol group(group C),nimodipine group(group D)and mannitol plus nimodipine group(group E).Terminal Deoxynucleotide Transferase-mediated dUTP Nick-end Labeling (TUNEL) and TBA were used respectively to measure the amount of apoptotic cells and the content of malondialdehyde(MDA) in brain tissues. RESULTS:① In the group B, the number of apoptotic cells was(46.6± 11.0) per visual field and the MDA content was(0.75± 0.07)ì mol/g, both significantly h igher than those of the group A(t=10.10, 15.43, P< 0.01).② The number of apopto tic cells and the content of MDA in the group C,D and E,especially in the group E,were all decreased compared with those of the group B(P< 0.05). CONCLUSION:Mannitol, nimodipine and especially combined use of both mannitol and nimodipine have neuroprotective effects on focal ischemia and reperfusion by decreasing the content of MDA and inhibiting cell apoptosis in brain tissue,whi ch is beneficial in guiding the clinical treatment of cerebral ischemic diseases .