PMID- 29762840 OWN - NLM STAT- MEDLINE DCOM- 20191022 LR - 20191022 IS - 2284-0729 (Electronic) IS - 1128-3602 (Linking) VI - 22 IP - 8 DP - 2018 Apr TI - The effect of miR-146a gene silencing on drug-resistance and expression of protein of P-gp and MRP1 in epilepsy. PG - 2372-2379 LID - 14829 [pii] LID - 10.26355/eurrev_201804_14829 [doi] AB - OBJECTIVE: To investigate the effect of miR-146a gene silencing on brain tissue and related drug-resistance proteins in rats and explore its resistance mechanism. MATERIALS AND METHODS: A rat model of chronic refractory epilepsy was established. The rats were divided into four groups: Normal group, Model group, Negative control group and AntagomiR-146a group. Hematoxylin and eosin (HE) stain was used to detect brain histopathological changes. We examined the expression of mRNA of miR-146a, multidrug resistance (MDR1) and multidrug-resistant associated protein (MRP1) by RT-PCR. The expressions of protein of High motility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear transcription factor-kappaB (NF-kappaB) pathway and P-glycoprotein (P-gp), MRP1 were detected by Western-blotting. RESULTS: We demonstrated that the pathological lesion was lighter in antagomiR-146a group compared with the model group. The mRNA expression of miR-146a in AntagomiR-146a group was significantly decreased compared to the model group. Furthermore, the mRNA expression of MDR1 and MRP1 in AntagomiR-146a group was lower than that in the model group. In addition, the protein expression of HMGB1, TLR4, NF-kappaB and P-gp, MRP1 in AntagomiR-146a group was lower than that in model group. CONCLUSIONS: These results demonstrated that miR-146a gene silencing can attenuate pathological changes and improve drug resistance in refractory epilepsy. Also, it is closely related to the HMGB1/TLR4/NF-kappaB signaling pathway regulation. FAU - Zhang, H-L AU - Zhang HL AD - Department of Neurology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China. qichen201612@126.com. FAU - Lin, Y-H AU - Lin YH FAU - Qu, Y AU - Qu Y FAU - Chen, Q AU - Chen Q LA - eng PT - Journal Article PL - Italy TA - Eur Rev Med Pharmacol Sci JT - European review for medical and pharmacological sciences JID - 9717360 RN - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1) RN - 0 (Antagomirs) RN - 0 (HMGB1 Protein) RN - 0 (MIRN146a microRNA, rat) RN - 0 (MicroRNAs) RN - 0 (Multidrug Resistance-Associated Proteins) RN - 0 (NF-kappa B) RN - 0 (Toll-Like Receptor 4) RN - Y49M64GZ4Q (multidrug resistance-associated protein 1) SB - IM MH - ATP Binding Cassette Transporter, Subfamily B, Member 1/*metabolism MH - Animals MH - Antagomirs/metabolism MH - Disease Models, Animal MH - Epilepsy/metabolism/*pathology MH - Gene Silencing MH - HMGB1 Protein/metabolism MH - MicroRNAs/antagonists & inhibitors/genetics/*metabolism MH - Multidrug Resistance-Associated Proteins/*metabolism MH - NF-kappa B/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction MH - Toll-Like Receptor 4/metabolism EDAT- 2018/05/16 06:00 MHDA- 2019/10/23 06:00 CRDT- 2018/05/16 06:00 PHST- 2018/05/16 06:00 [entrez] PHST- 2018/05/16 06:00 [pubmed] PHST- 2019/10/23 06:00 [medline] AID - 14829 [pii] AID - 10.26355/eurrev_201804_14829 [doi] PST - ppublish SO - Eur Rev Med Pharmacol Sci. 2018 Apr;22(8):2372-2379. doi: 10.26355/eurrev_201804_14829.