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.
作者
颜博
岳宗伟
李华坚
黄优
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)
出处
《免疫学杂志》
CAS
CSCD
北大核心
2022年第1期59-66,共8页
Immunological Journal
