The effect of miR-146a gene silencing on drug-resistance and expression of protein of P-gp and MRP1 in epilepsy

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-κB (NF-κB) 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-κB 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-κB signaling pathway regulation.

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