雷洛昔芬通过抑制神经细胞凋亡保护脑缺血大鼠脑细胞的机制研究  

Mechanisms of raloxifene protecting brain cells from cerebral ischemia in rats by inhibiting neuronal apoptosis

作　　者：管萍[1] 刘文娟 卢鹏超 李志红[1] GUAN Ping;LIU Wenjuan;LU Pengchao(Tianmen First People’s Hospital Hubei,Tianmen 431700,China)

机构地区：[1]天门市第一人民医院,湖北天门431700

出　　处：《中风与神经疾病杂志》2019年第4期322-326,共5页Journal of Apoplexy and Nervous Diseases

摘　　要：目的 探讨雷洛昔芬通过抑制神经细胞凋亡保护脑缺血大鼠脑细胞的机制。方法 建立大鼠大脑中动脉栓塞模型,分离培养大鼠海马组织,通过神经元加钙实验测定雷洛昔芬对神经元的保护性,通过Western-blot测定凋亡相关蛋白表达量,利用RT-PCR测定血液miRNA-21、miRNA-29因子表达水平。结果 雷洛昔芬中、高剂量组荧光强度显著降低(P <0. 05);与雷洛昔芬低价量组相比,雷洛昔芬中、高剂量组细胞增殖率显著增加,细胞miRNA-21和miRNA-29表达量显著降低(P <0. 001);雷洛昔芬组细胞caspase-3、Apaf-1蛋白均显著低于空白组与假手术组(P <0. 001);与雷洛昔芬低价量组相比,雷洛昔芬中、高剂量组细胞的caspase-3、Apaf-1蛋白显著增加(P<0. 001)。结论 雷洛昔芬通过抑制神经细胞凋亡蛋白caspase-3、Apaf-1及miRNA-21,miRNA-29的表达保护脑缺血大鼠脑细胞。Objective To explore the mechanism of raloxifene protecting cerebral cells of rats with cerebral ischemia by inhibiting neuronal apoptosis.Methods Rat middle cerebral artery embolism model was established,rat hippocampus tissue was isolated and cultured,the protective effect of raloxifene on neurons was determined by adding calcium to neurons,the expression of apoptosis-related eggs was determined by Western blot,and the expression levels of microRNA21 and microRNA29 in blood were determined by RT-PCR.Result The fluorescence intensity of raloxifen medium-dose group and high-dose group decreased significantly(P<0.05).Compared with the low-dose group,the cell proliferation rate increased significantly,the expression of microRNA-21 and microRNA-29 decreased significantly in the middle-dose group and the high-dose group(P<0.01).The results of apoptosis-related proteins showed that caspase-3 and Apaf-1 proteins in raloxifen group were significantly lower than those in blank group and sham-operated group(P<0.001);compared with low-dose group,caspase-3 and Apaf-1 proteins were significantly higher in the middle-dose group and the high-dose group(P<0.05).Conclusion Raloxifene can protect brain cells from cerebral ischemia by inhibiting the expression of caspase 3,Apaf-1,microRNA-21 and microRNA-29.

关 键 词：雷洛昔芬 神经细胞 凋亡蛋白 脑缺血 

分 类 号：R743.3[医药卫生—神经病学与精神病学]