Tetramethylpyrazine ameliorates isofluraneinduced cognitive dysfunction by inhibiting neuroinflammation via miR150 in rats

Tetramethylpyrazine (TMP) has neuroprotective effects in the pathogenesis of some human diseases, such as Parkinson's disease. The present study aimed to investigate the role of TMP in isofluraneinduced cognitive dysfunction in rats, and further identify the mechanisms involved in the protective effects of TMP. The Morris water maze test was used to evaluate the cognitive function of rats exposed to isoflurane or treated with TMP. ELISA was conducted to evaluate the effects of isoflurane or TMP on neuroinflammation. The expression of microRNA150 (miR150) was measured using reverse transcriptionquantitative PCR, and the potential target genes of miR150 were predicted and verified. The impaired cognitive function induced by isoflurane in the rats was significantly ameliorated by treatment with TMP. In addition, TMP treatment in rats attenuated neuroinflammation caused by isoflurane. The expression of miR150 was inhibited by isoflurane exposure, but was enhanced by TMP treatment in rats. Furthermore, the overexpression of miR150 alleviated the isofluraneinduced cognitive dysfunction and neuroinflammation, while the neuroprotective effects of TMP were significantly abrogated by the knockdown of miR150. AKT3 was a direct target of miR150, and its mRNA expression was significantly decreased by the overexpression of miR150 in isoflurane and TMPtreated rats. These results demonstrated the protective effects of TMP against isofluraneinduced cognitive dysfunction, which were achieved by attenuating neuroinflammation via the regulation of the miR150/AKT3 pathway. In addition, miR150 may serve as a novel therapeutic target for the alleviation of cognitive dysfunction induced by anesthetics.