基于基因芯片技术研究定痫丸对氯化锂-匹罗卡品致痫小鼠海马组织miRNA-187表达的影响
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摘要
目的:研究定痫丸对氯化锂-匹罗卡品致痫小鼠海马组织miRNA-187表达的影响。方法:采用基因芯片技术筛选出氯化锂-匹罗卡品致痫小鼠海马组织差异表达基因,并运用q-PCR技术验证其差异性表达。予定痫丸悬混液灌胃,运用q-PCR技术检测定痫丸悬混液对癫痫小鼠海马组织差异基因的表达。结果:通过基因芯片筛选出癫痫小鼠海马组织中差异表达miRNA下调18个,上调10个。筛选出miRNA-187,运用q-PCR技术验证了其表达下调(P<0.05)。经定痫丸悬混液干预后,发现癫痫小鼠海马组织miRNA-187表达上调(P<0.05)。结论:定痫丸可能通过上调miRNA-187对癫痫起到治疗作用,初步揭示定痫丸治疗癫痫的分子机制。
Objective:To study the effect of Dingxian Pills on the expression of miRNA-187 in hippocampus of LiCl-Pilocarpine-induced epilepsy mice. Methods: The differentially expressed genes in the hippocampus of mice with lithium chloride-pilocarpine-induced epilepsy were screened by gene chip technique and their differential expression was verified by q-PCR. The intervention of Dingxian Pills were intragastrically administered and q-PCR was used to detect the expression of differentially expressed genes in the hippocampus of epileptic mice. Results: Eighteen differentially expressed miRNAs and 10 up-regulated miRNAs were detected in the hippocampus of epileptic mice by microarray. The miRNA-187 was screened and its expression was down-regulated by q-PCR(P<0.05). After intervention of Dingxian Pills suspension, the expression of miRNA-187 in the hippocampus of epileptic mice was found to be upregulated(P<0.05). Conclusion: Dingxian Pills may play a therapeutic role in epilepsy by up-regulating miRNA-187, and initially reveal the molecular mechanism of epilepsy treated by Dingxian Pills.
Objective:To study the effect of Dingxian Pills on the expression of miRNA-187 in hippocampus of LiCl-Pilocarpine-induced epilepsy mice. Methods: The differentially expressed genes in the hippocampus of mice with lithium chloride-pilocarpine-induced epilepsy were screened by gene chip technique and their differential expression was verified by q-PCR. The intervention of Dingxian Pills were intragastrically administered and q-PCR was used to detect the expression of differentially expressed genes in the hippocampus of epileptic mice. Results: Eighteen differentially expressed miRNAs and 10 up-regulated miRNAs were detected in the hippocampus of epileptic mice by microarray. The miRNA-187 was screened and its expression was down-regulated by q-PCR(P<0.05). After intervention of Dingxian Pills suspension, the expression of miRNA-187 in the hippocampus of epileptic mice was found to be upregulated(P<0.05). Conclusion: Dingxian Pills may play a therapeutic role in epilepsy by up-regulating miRNA-187, and initially reveal the molecular mechanism of epilepsy treated by Dingxian Pills.
引文
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[22] Li Y, Shan X, Wu Z, et al. IDH1 mutation is associated with a higher preoperative seizure incidence in low-grade glioma: A systematic review and meta-analysis[J]. Seizure,2018,55(16):76-82.
[23] 高未华,樊锐太. MicroRNA-187在胶质瘤中的表达及对预后判断的价值[J]. 河南医学研究,2017,26(8):1364-1366.
[24] 张素雅,韩燕. 癫痫鼠电击下颞叶相关miRNA(miR-187)表达谱的下调表达[J]. 中国妇幼健康研究,2017(S2):675-676.
[26] Haenisch S, Von Ruden EL, Wahmkow H, et al.miRNA-187-3p-Mediated Regulation of the KCNK10/TREK-2 Potassium Channel in a Rat Epilepsy Model[J]. ACS Chem Neurosci,2016,7(11):1585-1594.
[27] 李炳照.实用中医方剂双解与临床[M].北京:科学技术文献出版社,2008:615.
[2] Li R, Liao W, Yu Y, et al. Differential patterns of dynamic functional connectivity variability of striato-cortical circuitry in children with benign epilepsy with centrotemporal spikes[J]. Hum Brain Mapp,2018,39(3):1207-1217.
[3] 刁丽梅,陈子蓉,黄东红,等.左侧颞叶癫痫患者执行功能损害与钩束弥散张量成像参数的相关性[J].中国神经精神疾病杂志,2013,39(8):474-478.
[4] Yang H, Zhang C, Liu C, et al. Brain network alteration in patients with temporal lobe epilepsy with cognitive impairment[J]. Epilepsy Behav, 2018,9(81):41-48.
[5] Zhang C, Yang H, Qin W, et al. Characteristics of resting-statefunctional connectivity in intractable unilateral temporal lobe epilepsy patientswith impaired executive control function[J]. Front Hum Neurosci ,2017,11(99):1871-1880.
[6] 秦兵,廖卫平,臼井直敬,等.癫痫:全球重点防治的神经精神疾病[J].实用医学杂志,2012,28(13):2109.
[7] Van Vliet EA, Puhakka N, Mills JD, et al.Standardization procedure for plasma biomarker analysis in rat models of epileptogenesis: Focus on circulating microRNAs[J]. Epilepsia,2017,58(12):2013-2020.
[8] 凌小林.癫痫患者婚姻生育情况国内研究现状[J].现代医药卫生,2013,29(14):2160.
[9] Kleen JK, Scott RC, Lenck-Santini PP, et al. Cognitive and behavioral Co-Mo rbidities of epilepsy[J].Jasper’s Basic Mechanisms of the Epilepsies, 2012,22(14):915-929.
[10] 程国彭.医学心悟[M].北京:人民卫生出版社,1959:140.
[11] 吴琼,刁丽梅.定痫丸治疗癫痫的研究新进展[J].中医临床研究,2017,9(1):40-42.
[12] Berezikov E, Van Tetering G, Verheul M, et al. Many novel mammalian microRNA candidates identified by extensive cloning and RAKE analysis[J]. Genome Res,2006,16(10):1289-1298.
[13] Qiu L, Tan EK, Zeng L. microRNAs and Neurodegenerative Diseases[J]. Adv Exp Med Biol,2015,888(29):85-105.
[14] Karthikeyan A, Patnala R, Jadhav SP, et al. MicroRNAs: Key Players in Microglia and Astrocyte Mediated Inflammation in CNS Pathologies[J]. Curr Med Chem, 2016,23(30):3528-3546.
[15] Racine RJ. Modification of seizure activity by electrical stimulation: II.Motor seizures[J]. Electroencephalogr Clin Neurophysiol,1972,32(3):281-294.
[16] Alsharafi WA, Xiao B, Abuhamed MM, et al.Correlation Between IL-10 and microRNA-187 Expression in Epileptic Rat Hippocampus and Patients with Temporal Lobe Epilepsy[J]. Front Cell Neurosci,2015,9(54):466.
[17] Bot AM, Debski KJ, Lukasiuk K. Alterations in miRNA levels in the dentate gyrus in epileptic rats[J]. PLoS One, 2013,8(10):e76051.
[18] Rossato M, Curtale G, Tamassia N, et al. IL-10-induced microRNA-187 negatively regulates TNF-α, IL-6, and IL-12p40 production in TLR4-stimulated monocytes[J]. Proc Natl Acad Sci USA,2012,109(45):E3101-E3110.
[19] Srivastava PK, Roncon P, Lukasiuk K, et al. Meta-Analysis of MicroRNAs Dysregulated in the Hippocampal Dentate Gyrus of Animal Models of Epilepsy[J]. eNeuro,2017,4(6):223-234.
[20] Tao H, Zhao J, Liu T, et al. Intranasal Delivery of miR-146a Mimics Delayed Seizure Onset in the Lithium-Pilocarpine Mouse Model[J]. Mediators Inflamm,2017,17(12):651-661.
[21] Ambrogini P, Albertini MC, Betti M, et al. Neurobiological Correlates of Alpha-Tocopherol Antiepileptogenic Effects and MicroRNA Expression Modulation in a Rat Model of Kainate-Induced Seizures[J]. Mol Neurobiol,2018,2(22):1553-1561.
[22] Li Y, Shan X, Wu Z, et al. IDH1 mutation is associated with a higher preoperative seizure incidence in low-grade glioma: A systematic review and meta-analysis[J]. Seizure,2018,55(16):76-82.
[23] 高未华,樊锐太. MicroRNA-187在胶质瘤中的表达及对预后判断的价值[J]. 河南医学研究,2017,26(8):1364-1366.
[24] 张素雅,韩燕. 癫痫鼠电击下颞叶相关miRNA(miR-187)表达谱的下调表达[J]. 中国妇幼健康研究,2017(S2):675-676.
[26] Haenisch S, Von Ruden EL, Wahmkow H, et al.miRNA-187-3p-Mediated Regulation of the KCNK10/TREK-2 Potassium Channel in a Rat Epilepsy Model[J]. ACS Chem Neurosci,2016,7(11):1585-1594.
[27] 李炳照.实用中医方剂双解与临床[M].北京:科学技术文献出版社,2008:615.
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