RESUMEN
Objective To study the preventive effect of microinsulin on cognitive dysfunction induced by sevoflurane inhalation anesthesia in rats and its possible mechanism. Methods Sixty newborn rats were randomly divided into control group (CON), insulin prevention low dose group (LIP), insulin prevention hihg dose group (HIP), and sevoflurane model group (MOD). The prevention group and the model group were induced by sevoflurane to construct rat cognitive dysfunction model. Morris water maze directional sailing test and space exploration test were used to evaluate the learning and memory function of rats; HE staining was used to observe the pathological morphological changes of hippocampus in rats; Flow cytometry was used to detect the hippocampus of rats cell apoptosis; Detection of rapamycin target protein (mTOR) and eukaryotic peptide chain elongation factor 2 (eEF-2) mRNA levels in hippocampus by RT-PCR; The expression levels of brain-derived neurotrophic factor (BDNF), post-synaptic dense protein-95 (PSD-95), synapsin- I, and calmodulin kinase II α (CaMK II α), mTOR and eEF-2 protein were detected by Western blotting. Results The result of the Morris water maze experiment showed that insulin significantly reduced the escape latency and swimming distance of rats, and increased the number of crossing platforms; Flow cytometry result showed that the insulin prevention group significantly inhibited the apoptosis of rat brain neurons, and the inhibition effect of high-dose insulin prevention group was more obvious; RT-PCR and Western blotting analysis found that the expression levels of mTOR and eEF-2 mRNA and proteins in the hippocampus of the model group increased significantly, while the expression levels of BDNF, PSD-95, synapsin- I, and CaMK II α proteins reduced significantly. The expression levels of mTOR and eEF-2 mRNA and proteins in the hippocampus of rats in the insulin prevention group decreased significantly, while the expression levels of BDNF, PSD-95, synapsin- I, and CaMK II α protein increased significantly. The difference was statistically significant (P < 0.05). Conclusion Trace insulin can increase the expression of synapse-related proteins in the hippocampus of cognitive dysfunction rats, reduce their mTOR and eEF-2 mRNA expression levels, and prevent sevoflurane-induced cognitive impairment in rats. The mechanism may be related to the regulation of mTOR-eEF-2 approach.