Abstract：Objective: To study the intervening effect of dexmedetomidine on hepatic ischemia/reperfusion injury rat model via PI3K/AKT/CREB signaling pathway. Methods: A total of 80 SPF SD rats underwent ischemia/reperfusion operation using a clamp occluding left portal and medial portal triad veins for 30 min, and then were randomly divided into a sham operation group (Sham), a model group (Model), a low-dose dexmedetomidine group (Dex-L), and a dexmedetomidine high-dose group (Dex-H); 10 animals sacrificed after reperfusion for 6h and 12h in each group. In the sham operation group, anesthesia followed by laparotomy was done withnot blocking the liver blood flow. The Dex-H group was intraperitoneally injected with 100μg/kg dexmedetomidine; the Dex-L group was intraperitoneally injected with 50μg/kg dexmedetomidine; the sham operation group and the model group were injected with solvent only. Automatic blood biochemical analyzer was used to detect serum Aspartate aminotransferase(AST) and Alanine aminotransferase(ALT) levels; HE staining was used to observe liver pathological changes; biochemical kits were used to detect serum Glutathione (GSH), Malondialdehyde (MDA), Superoxide dismutase (SOD)levels; Western Blot was used to detect PI3K, pAKT, AKT, CREB levels; PCR was used to detect the expressions of BAX and Bcl2. Results: Compared with the sham group, the serum ALT and AST levels in the model group significantly increased at different time points (P<0.05). Compared with the model group, the levels of ALT and AST after the intervention of different doses of dexmedetomidine both significantly reduced (P<0.05). The liver cells in the model group showed obvious swelling and degeneration, and the structure of the liver lobules was disordered. After 6 and 12 hours of intervention with different doses of dexmedetomidine, the liver pathology was improved, and the liver MDA level was significantly lower than that in the model group(P<0.05). The level of GSH significantly increased (P<0.05). Western blot results showed that compared with the model group, different doses of dexmedetomidine intervention for 6 and 12 hours, PI3K, phosphorylated AKT and CREB all significantly increased (P<0.05). The PCR results showed that compared with the model group, different doses of dexmedetomidine intervention for 6 and 12 hours and the expression of BAX significantly reduced (P<0.05), and the expression of Bcl2 significantly increased (P<0.05). Conclusion: Dexmedetomidine can significantly improve the serum and pathological indicators in hepatic I/R injury model rats, and inhibit oxidative stress and apoptosis Its mechanism may be related to the activation of PI3K/AKT/CREB signaling.
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2022, Vol. 28 
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