Objective  To investigate the protective effect and mechanism of butylphthalide on cisplatin-induced cell injury in rat adrenal medullary pheochromocytoma (PC12) based on phosphatidylinositol-3-kinase/Akt/cAMP response element binding protein (PI3K/Akt/CREB) pathway.

Methods  Different concentrations of butylphthalide and cisplatin cell culture medium were applied to PC12 cells, and the cell activity was detected by CCK-8 method. According to the results of CCK-8 investigation, the subsequent experiments were divided into the blank control group, the cisplatin group (50  μmol/ L), and low, medium and high dose groups of butylphthalein (25, 50, 100 μmol/L). ELISA kit was used to detect the levels of intracellular interleukin-6 (IL-6) and interleukin-1β (IL^-1β), TUNEL staining was used to detect apoptosis, and the expressions of PI3K/Akt/CREB pathway-related proteins PI3K, p-PI3K, Akt, p-Akt, CREB and p-CREB were detected by Western blotting.

Results  Compared with the cisplatin group, butylphthalein could increase the viability of PC12 cells to varying degrees, but the difference was not statistically significant (P>0.05). The ELISA results showed that compared with the control group, cisplatin could significantly increase the levels of IL-6 and IL^-1β (P<0.05); compared with the cisplatin group, butylphthalein could reduce the levels of IL-6 and IL^-1β, with a statistically significant difference in the high-dose group (P<0.05). The TUNEL results showed that compared with the control group, the cisplatin group significantly increased the apoptosis rate of PC12 cells (P<0.05); after administration of butylphthalein, the degree of cell apoptosis was significantly reduced (P<0.05). Western blotting results showed that compared with the control group, the p-PI3K/PI3K, p-Akt/Akt, and p-CREB/CREB protein levels of PC12 cells in the cisplatin group were reduced, with statistically significant differences in p-Akt/Akt and p-CREB/CREB protein levels (P<0.05); compared with the cisplatin group, the p-PI3K/PI3K in all dose groups, p-Akt/Akt in the medium and low dose groups, and p-CREB/CREB protein levels in the medium dose group of PC12 cells were significantly increased (P<0.05).

Conclusion  Butrimlphthalein can improve the survival rate of PC12 cells, reduce cell inflammation, inhibit apoptosis, and play a protective role in cisplatin-induced neurocytotoxicity through PI3K/Akt/CREB signaling pathway.

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