钩藤碱调控微小RNA-181a抑制甲基苯丙胺大鼠肾上腺嗜铬细胞瘤细胞成瘾的研究  

Rhynchophylline inhibits methamphetamine-induced addiction in rat pheochromocytoma cells by regulating micro RNA-181a

作　　者：江明金[1] 王珠 吕燕妮[3] 胡建兰 胡锦芳[3] JIANG Ming-jin;WANG Zhu;LüYan-ni;HU Jian-lan;HU Jin-fang(Jiangxi Provincial Institute of Translational Medicine,The First Affiliated Hospital of Nanchang University;Key Laboratory of Malignant Tumor,Jiangxi Academy of Traditional Chinese Medicine;Department of Pharmacy,The First Affiliated Hospital of Nanchang University)

机构地区：[1]南昌大学第一附属医院江西省转化医学研究院,江西南昌330006 [2]江西省中医药研究院恶性肿瘤重点研究室,江西南昌330077 [3]南昌大学第一附属医院药学部,江西南昌330077

出　　处：《中国临床药理学杂志》2022年第17期2055-2059,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81760724);江西省自然科学基金资助项目(20171BAB215067,20181BAB205026);江西省教育厅科技基金资助项目(GJJ160129);江西省卫健委科技基金资助项目(20181044);江西省中医药管理局科技基金资助项目(2017A287)。

摘　　要：目的 探讨钩藤碱对甲基苯丙胺成瘾大鼠肾上腺嗜铬细胞瘤(PC12)细胞模型中微小RNA-181a(miR-181a)表达的影响。方法 将细胞分为9组:正常组、模型组、对照组、实验组、antagomiR negative control组((1)组)、miR-181a antagomiR组((2)组)、antagomiR negative control+甲基苯丙胺组((3)组)、miR-181a antagomiR+甲基苯丙胺组((4)组)和miR-181a antagomiR+钩藤碱+甲基苯丙胺组((5)组)。用实时荧光聚合酶链反应检测miR-181a的表达水平,用Western blot法检测A型γ-氨基丁酸受体α1亚基(GABRA1)蛋白的表达水平。结果 正常组、模型组、对照组、实验组、(1)组、(2)组、(3)组、(4)组和(5)组的miR-181a相对表达量分别为1.00±0.00,2.39±0.26,1.02±0.12,1.07±0.15,1.00±0.00,0.32±0.04,2.30±0.25,1.68±0.20和1.45±0.17;正常组、模型组、对照组、实验组、(1)组、(3)组、(4)组和(5)组的GABRA1蛋白相对表达量分别为1.00±0.00,0.54±0.06,0.98±0.12,0.91±0.12,1.00±0.00,0.53±0.06,0.88±0.09和0.92±0.11。与正常组相比,模型组的miR-181a表达升高、GABRA1蛋白表达降低,差异均有统计学意义(均P<0.01);与模型组相比,实验组的miR-181a表达降低、GABRA1蛋白表达升高,差异均有统计学意义(均P<0.01);与(3)组相比,(4)组的miR-181a表达降低、GABRA1蛋白表达升高,差异均有统计学意义(均P<0.01)。结论 钩藤碱可能通过调控miR-181a/GABRA1轴抑制甲基苯丙胺PC12细胞成瘾。Objective To investigate the effect of rhynchophylline on the expression of microRNA-181 a(miR-181 a) in methamphetamine-induced addiction in rat pheochromocytoma(PC12) cells.Methods PC12 cells were randomly divided into 9 groups as follows:normal,model,control,experimental,antagomiR negative control((1)),miR-181 a antagomir((2)),antagomiR negative control+methamphetamine((3)),miR-181 a antagomiR+methamphetamine((4)) and miR-181 a antagomiR+rhynchophylline+methamphetamine((5)) groups.The expression of miR-181 a was measured by Real-time PCR and the expression of γ-aminobutyric acid A receptor α1-subunit(GABRA1) protein was determined by Western blot in PC12 cells.Results The relative expressions of miR-181a in the normal,model,control experimental,(1),(2),(3),(4) and(5) groups were 1.00 ± 0.00,2.39 ± 0.26,1.02 ± 0.12,1.07 ± 0.15,1.00 ± 0.00,0.32 ± 0.04,2.30 ± 0.25,1.68 ± 0.20 and 1.45 ± 0.17,respectively.The relative expressions of GABRA1 protein in the normal,model,control,experimental,(1),(3),(4) and(5) groups were 1.00 ± 0.00,0.54 ± 0.06,0.98 ± 0.12,0.91 ± 0.12,1.00 ± 0.00,0.53 ± 0.06,0.88 ± 0.09 and 0.92 ± 0.11,respectively.Compared with the normal group,the expression of mi R-181a was increased and the expression of GABRA1 protein was decreased in the model group in PC12 cells,with statistical significances( all P < 0.01);compared with the model group,the expression of mi R-181a was decreased and the expression of GABRA1 protein was increased in the experimental group in PC12 cells,with statistical significances( all P < 0.01);compared with the(3) group,the expression of mi R-181a was decreased and the expression of GABRA1 protein was increased in the(4) group in PC12cells,with statistical significances( all P < 0.01).Conclusion Rhynchophylline might inhibit methamphetamine-induced addiction in PC12 cells by regulating the mi R-181a/GABRA1 axis.

关 键 词：甲基苯丙胺 微小RNA-181a 钩藤碱 大鼠肾上腺嗜铬细胞瘤细胞 成瘾 A型γ-氨基丁酸受体α1亚基 

分 类 号：R971.7[医药卫生—药品]