Department of Neurology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
Eur Rev Med Pharmacol Sci. 2018 Apr;22(8):2372-2379. doi: 10.26355/eurrev_201804_14829.
To investigate the effect of miR-146a gene silencing on brain tissue and related drug-resistance proteins in rats and explore its resistance mechanism.
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-κB (NF-κB) pathway and P-glycoprotein (P-gp), MRP1 were detected by Western-blotting.
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-κB and P-gp, MRP1 in AntagomiR-146a group was lower than that in model group.
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-κB signaling pathway regulation.
研究 miR-146a 基因沉默对大鼠脑组织及相关耐药蛋白的影响，探讨其耐药机制。
建立慢性难治性癫痫大鼠模型。将大鼠分为四组：正常组、模型组、阴性对照组和 AntagomiR-146a 组。苏木精-伊红（HE）染色检测脑组织病理变化。采用 RT-PCR 检测 miR-146a、多药耐药（MDR1）和多药耐药相关蛋白 1（MRP1）mRNA 的表达。采用 Western-blotting 检测高迁移率族蛋白 1（HMGB1）/Toll 样受体 4（TLR4）/核转录因子-κB（NF-κB）通路及 P-糖蛋白（P-gp）、MRP1 蛋白的表达。
AntagomiR-146a 组的病理损伤较模型组减轻。AntagomiR-146a 组 miR-146a 的 mRNA 表达明显低于模型组。此外，AntagomiR-146a 组 MDR1 和 MRP1 的 mRNA 表达低于模型组。而且，AntagomiR-146a 组 HMGB1、TLR4、NF-κB 和 P-gp、MRP1 蛋白的表达低于模型组。
miR-146a 基因沉默可减轻难治性癫痫的病理变化，改善耐药性，与 HMGB1/TLR4/NF-κB 信号通路的调节密切相关。
