| Objective:This study aimed to investigate the involvement of miRNAs in the development of TLE, the association of miR-153 with TPM treatment and the inhibition function of TPM on apoptosis in TLE.Methods:Li-pilocarpine was used for induction of epilepsy and 80 rats were divided into four groups randomly:1) control,2) TLE group,3) low dose TPM group (40 mg/kg), and 4) high dose TPM group (80 mg/kg). MiRNAs profiling in hippocampus of four groups was detected using gene chip microarray analysis, the morphological changes of hippocampus were observed using H&E staining, and the expression level of caspase-3 protein in hippocampus was detected by western blot and immunohistochemistry (IHC).Results:A total of 10 miRNAs (miR-183,-204,-210,-339,-34b,351,-429,-455,466b,-503) were up-regulated and 13 miRNAs (miR-153,-451,-101a,-488,-300,-34a,-380,-592,-598,-741,-7b,-374,-9) were down-regulated in TLE rat models compared with control rats. Importantly, these 10 up-regulated miRNAs were down-regulated, and the 13 down-regulated miRNAs were up-regulated in both low dose and high dose TPM-treated groups. Of these, miR-153 underwent the greatest change in regulation, indicating that TPM treatment is associated with down-regulation of miR-153 expression and with higher dose of TPM, the up-regulation of miR-153 is more significantly. Caspase-3 was significantly up-regulated in the TLE group, but down-regulated in TPM-treated groups, especially in the high dose group, suggesting that TPM could inhibit the apoptosis of cells in the hippocampus of epilepsy by down-regulating caspase-3 expression and with the higher dose of TPM, the drug efficacy is better.Conclusions:1) miRNAs is involved in the development of TLE and miR-153 could be a new therapeutic target in TPM treatment.2) miR-153 is involved in the development of TLE and TPM treatment could up-regulate miR-153.3) TPM could inhibit the apoptosis in hippocampus of TLE rats, and with the higher dose of TPM, the drug efficacy is better. |
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