右美托咪定对抗化学性低氧引起神经细胞的损伤及其机制

目的探讨α2肾上腺素能受体激动剂右美托咪定(dexmedetomidine,Dex)是否通过抑制p38MAPK通路保护PC12细胞对抗化学性低氧引起的损伤。方法应用化学性低氧模拟剂氯化钴(CoCl2)处理PC12细胞以建立化学性低氧损伤神经细胞模型。采用Western blot法测定p38MAPK蛋白的表达水平,CCK-8比色法检测细胞存活率,Hoechst 33258核染色法观察细胞凋亡的形态学及数量改变,罗丹明123染色荧光显微镜照相测定线粒体膜电位(MMP)。结果在60～180 min的时间范围内,600μmol/L CoCl2处理PC12细胞后明显地促进磷酸化p38MAPK表达;在120 min,p38MAPK表达量达到高峰;400μmol/L Dex不仅能保护PC12细胞对抗CoCl2引起的细胞毒性、致凋亡作用及MMP损伤作用,还能抑制CoCl2对p38MAPK表达的上调作用;p38MAPK抑制剂SB203580能模拟Dex的抗化学性低氧损伤的神经保护作用,使细胞存活率升高,凋亡细胞数量减少及MMP升高。结论 Dex能保护神经细胞对抗化学性缺氧引起的损伤,抑制p38MAPK通路可能是其作用机制之一。

The protection of dexmedetomidine against chemical hypoxia-induced neurons injury and its mechanism

Objective To investigate whether α2-adrenoreceptor agonist dexmedetomidine(Dex) protects PC12 cells against chemical hypoxia-induced injury by inhibiting p38MAPK pathway.Methods PC12 cells were treated with cobalt chloride(CoCl2) to establish a model of chemical hypoxia-induced neuronal injury.Expression of p38 mitogen-activated protein kinase(MAPK) protein was measured by Western blot assay.Cell viability was assessed by cell counter kit(CCK-8).The changes in morphology and the apoptotic cell count were observed by Hoechst 33258 staining.Mitochondrial membrane potential(MMP) was measured by rhodamine123 staining and photofluorography.Results Exposure of PC12 cells to 600 μmol/L CoCl2 significantly enhanced the expression of phosphorylated(p) p38MAPK at the duration between 60 and 180 min,peaking at 120 min.Dex at 400 μmol/L not only protected PC12 cells against CoCl2-induced cytotoxicity,apoptotic effect and MMP damage,but also inhibited up-regulation of p-p38MAPK induced by CoCl2.SB203580,an inhibitor of p38MAPK,mimicked the neuroprotective effect of Dex against chemical hypoxia-induced injury,evidenced by increases in both cell viability and MMP,as well as decrease in apoptotic cells.Conclusion Dex can protect neuronal cells against chemical hypoxia-induced injury,inhibition of p38MAPK pathway may be one of the mechanisms responsible for this effect.