姜黄素降低局灶脑缺血/再灌注大鼠大脑皮质缺血半暗带神经元丢失

Curcumin reduces neuronal loss in the ischemic penumbra of cerebral cortex in focal cerebral ischemia/reperfusion rats

目的探讨姜黄素减轻局灶脑缺血/再灌注损伤的可能机制。方法将大鼠随机分为假手术组(sham)、模型组(tMCAO)和姜黄素组(Cur,100 mg/kg腹腔注射)(n=15)。于再灌注后24 h,用Longa评分评价大鼠神经功能;RT-qPCR检测大脑皮质缺血半暗带内Shh、Ptc和Smo mRNA含量;免疫荧光共聚焦检测大脑缺血半暗带内NeuN阳性细胞数量和Gli蛋白在细胞内分布。结果再灌注后24 h,Cur组大鼠Longa评分明显低于tMCAO组(P<0.05);Cur组大脑皮质缺血半暗带内NueN阳性神经元较tMCAO组明显增多(P<0.05);与sham相比,tMCAO组大脑皮质半暗带内Shh、Ptc和Smo mRNA表达明显升高(P<0.05),Cur组上述mRNA进一步升高(P<0.05);sham组缺血半暗带内Gli-1蛋白主要分布在细胞质,缺血后Gli-1蛋白部分转位至细胞核,Cur组Gli-1蛋白主要分布在细胞核。结论姜黄素治疗可促进局灶脑缺血/再灌注模型大鼠神经功能恢复,减少大脑皮质缺血半暗带内神经元丢失。

Objective To explore the possible mechanism of curcumin in ameliorating focal cerebral ischemia/reperfusion injury. Methods Rats were randomly divided into sham, model(tMCAO) and curcumin(Cur) group(100 mg/kg by intraperitoneal injection)(n=15). 24 hours after reperfusion, Longa score was used to evaluate neurological function, RT-qPCR was used to detect the level of Shh, Ptc and Smo mRNA in ischemic penumbra of cerebral cortex. The number of NeuN positive cell and intra-celluar distribution of Gli protein in the ischemic penumbra were assessed by immunofluorescence confocal technique. Results 24 hours after reperfusion, the Longa score in Cur group was significantly lower than that in tMCAO group(P<0.05). The number of NeuN positive cells in Cur group significantly increased than tMCAO group(P<0.05). The level of Shh, Ptc and Smo mRNA in tMCAO was higher than those in sham group(P<0.05), moreover, the mRNA mentioned above in Cur group was further increased(P<0.05). The Gli-1 protein in sham group mainly located in cytoplasm, and partially translocatedto nucleus in tMCAO group. The Gli-1 protein in Cur group mainly located in the nucleus. Conclusions Curcumin promoted the recovery of neurological function in focal cerebral ischemia/reperfusion rats and decreased the neuronal loss in the ischemic penumbra of cerebral cortex.