尼莫地平对颅脑损伤模型大鼠早期血管生成的影响及其机制研究

Effects of nimodipine on early angiogenesis in rat models of craniocerebral injury and its mechanism

摘要:

目的 探究尼莫地平通过Akt/ERK通路对颅脑损伤模型大鼠早期血管生成的影响及其作用机制。方法 25只SD雄性大鼠随机取8只作为对照组，其余大鼠复制颅脑损伤模型，1只模型复制失败，其余分为模型组和尼莫地平组，每组8只。尼莫地平组给予1 mg/（kg·d）尼莫地平，对照组和模型组均给予等量生理盐水。治疗7 d后，检测血管内皮细胞数及微血管密度（MVD），血清低氧诱导因子lα（HIF-lα）、促血管生成素2（Ang-2）水平，比较脑组织病理学变化及Akt/ERK通路蛋白相对表达量。结果 模型组、尼莫地平组大鼠神经功能评分高于对照组（P <0.05）；且模型组高于尼莫地平组（P <0.05）。模型组、尼莫地平组大鼠血管内皮细胞数和MVD多于对照组（P <0.05）；且模型组均少于尼莫地平组（P <0.05）。模型组、尼莫地平组大鼠PI3K、pAkt/Akt、（pERK1/2）/（ERK1/2）蛋白相对表达量高于对照组（P <0.05）；且模型组均低于尼莫地平组（P <0.05）。结论 尼莫地平能够促进颅脑损伤模型大鼠早期血管生成，其作用机制可能与Akt/ERK通路有关。

Abstract:

Objective To explore the effects of nimodipine on early angiogenesis in rat models with craniocerebral injury and its mechanism.Methods Eight of 25 male SD rats were randomly selected as the control group, and the rest rats were used to establish the craniocerebral injury models. Except the one that was unsuccessfully modeled, other rats were divided into model group and nimodipine group, with 8 rats in each group. The nimodipine group was given 1 mg/(kg?d) of nimodipine, while the control group and the model group were given the same amount of normal saline. After 7 days of treatment, the number of vascular endothelial cells, microvessel density (MVD), and hypoxia inducible factor-1α (HIF-Ⅰα) and angiopoietin-2 (Ang-2) levels were measured. The pathological changes of brain tissues and the protein expressions of Akt/ERK pathway-associated molecules were compared among the groups.Results The neurological scores of the model group and nimodipine group were higher relative to those of the control group (P < 0.05), and those of the model group were even higher than those of the nimodipine group (P < 0.05). The number of vascular endothelial cells and MVD in the model group and nimodipine group were higher than those in the control group (P < 0.05), and those in the model group were lower than those in the nimodipine group (P < 0.05). The protein levels of PI3K, pAkt/Akt, and (pERK1/2) / (ERK1/2) in the model group and nimodipine group were higher compared with the control group (P < 0.05), while those of the model group were lower than those of the nimodipine group (P < 0.05).Conclusions Nimodipine promotes early angiogenesis in rat models of craniocerebral injury, and its mechanism may be related to the Akt/ERK pathway.