抑制miR-133b通过靶向FOXP3对PD大鼠调节性T淋巴细胞、炎性反应和神经元凋亡的影响  

The effect of miR-133b inhibition by targeting FOXP3 on regulatory T lymphocytes,inflammatory response and neuronal apoptosis in PD rats

作　　者：颜博[1] 岳宗伟 李华坚 黄优[1] 高唯一 王改青 YAN Bo;YUE Zongwei;LI Huajian;HUANG You;GAO Weiyi;WANG Gaiqing(Department of Neurology,Hainan Third People's Hospital,Sanya 572000,China;Department of Neurology,Second Affiliated Hospital of Sun Yat-sen University,Guangzhou 510235,China)

机构地区：[1]海南省第三人民医院神经内科,三亚572000 [2]中山大学附属第二医院神经内科,广州510235

出　　处：《免疫学杂志》2022年第1期59-66,共8页Immunological Journal

摘　　要：目的探究抑制微小RNA(microRNA,miR)-133b通过靶向叉头盒蛋白3(forkhead box protein 3,FOXP3)对帕金森病(Parkinson's disease,PD)大鼠调节性T细胞(regulatory T cells,Treg)的影响。方法32只PD模型大鼠随机分为PD组和PD+miR-133b antagomir组(n=16),健康大鼠16只作为对照组。尾静脉注射miR-133b antagomir(300µg)来抑制miR-133b的水平。检测和比较各组大鼠神经功能、黑质损伤、细胞凋亡、炎性反应、Treg细胞水平、miR-133b、FOXP3 mRNA和蛋白表达水平;通过双荧光素酶报告验证miR-133b和FOXP3的靶向关系。结果PD组的逃避潜伏期、旋转速率、细胞凋亡情况、IL-6、miR133b水平显著高于对照组,穿越次数、IL-10、FOXP3 mRNA和蛋白表达量显著低于对照组(P<0.05)。PD+miR-133b antagomir组的逃避潜伏期、旋转速率、细胞凋亡情况、IL-6、miR-133b水平显著低于PD组,穿越次数、IL-10、FOXP3 mRNA和蛋白表达量显著高于PD组(P<0.05)。miR-133b可与FOXP3靶向结合,提高miR-133b的水平显著抑制FOXP3 mRNA和蛋白表达(P<0.05)。结论抑制miR-133b的水平会促进FOXP3蛋白的表达量,恢复PD大鼠模型中Treg水平,抑制黑质组织的炎性反应,缓解细胞凋亡,保护神经功能。This study was performed to explore the effect of microRNA(miR)-133b inhibition by targeting forkhead box protein 3(FOXP3)on regulatory T lymphocytes(Treg)in Parkinson's disease(PD)rats.Firstly,32 PD model rats were randomly divided into PD group and PD+miR-133b antagomir group(n=16),with another 16 healthy rats as control group.miR-133b antagomir(300µg)was injected into the tail vein to suppress the level of miR-133b.Then the nerve function,substantia nigra injury,apoptosis,inflammatory response,Treg cell level,miR133b,FOXP3 mRNA and protein expression levels were detected and compared.The targeting relationship between miR-133b and FOXP3 was verified by dual luciferase report.Data showed that the escape latency,rotation rate,apoptosis,IL-6 and miR-133b levels in PD group were significantly higher than those in the control group,while the number of crossings,IL-10,and FOXP3 mRNA and protein expression were significantly lower than those of the control group(P<0.05).miR-133b antagomir could significantly reverse these changes in PD group mentioned above(P<0.05).There was a targeted binding between miR-133b and FOXP3.Increasing the level of miR-133b significantly inhibited FOXP3 mRNA and protein expression(P<0.05).In conclusion,inhibiting the level of miR-133b will promote the expression of FOXP3 protein,restore the level of Treg,inhibit the inflammatory response of the substantia nigra tissue,relieve cell apoptosis,and protect nerve function in PD rats.

关 键 词：帕金森病 微小RNA-133b 叉头盒蛋白3 调节性T细胞 

分 类 号：R741.02[医药卫生—神经病学与精神病学]