右美托咪定基于PI3K/AKT/CREB信号通路对肝脏缺血再灌注损伤大鼠干预作用研究

doi:10.3969/j.issn.1006-6233.2022.02.03

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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.

Key words： Hepatic ischemia/reperfusion injury Dexmedetomidine PI3K/AKT/CREB signaling pathway

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2022.02.03 OR http://www.hbyxzzs.cn/EN/Y2022/V28/I2/189

[1] Li J,Li R J,Lv G Y,et al.The mechanisms and strategies to protect from hepatic ischemia-reperfusion injury [J].European Review for Medical and Pharmacological Sciences,2015,19(11):2036~2047.
[2] Guan L Y,Fu P Y,Li P D,et al.Mechanisms of hepatic ischemia-reperfusion injury and protective effects of nitric oxide [J].World Journal of Gastrointestinal Surgery,2014,6(7):122~128.
[3] Liu D Q,Chen S P,Sun J,et al.Berberine protects against ischemia-reperfusion injury:a review of evidence from animal models and clinical studies [J].Pharmacological Research,2019,148:104385.
[4] Takasu C,Vaziri N D,Li S,et al.Treatment with dimethyl fumarate ameliorates liver ischemia/reperfusion injury [J].World Journal of Gastroenterology,2017,23(25):4508~4516.
[5] Rampes S,Ma D.Hepatic ischemia-reperfusion injury in liver transplant setting:mechanisms and protective strategies [J].Journal of Biomedical Research,2019,33(4):221~234.
[6] Li A,Yuen V M,Goulay-dufay S,et al.Pharmacokinetics and pharmacodynamics of dexmedetomidine [J].Drug Development and Industrial Pharmacy,2016,42(12):1917~1927.
[7] Cai Y,Xu H,Yan J,et al.Molecular targets and mechanism of action of dexmedetomidine in treatment of ischemia/reperfusion injury [J].Molecular Medicine Reports,2014,9(5):1542~1550.
[8] Lim H,Kim T Y,Kim S Y,et al.The protective effects of dexmedetomidine preconditioning on hepatic ischemia/reperfusion injury in rats [J].Transp Proc,2021,53(1):427~435.
[9] Chai Y,Zhu K,Li C,et al.Dexmedetomidine alleviates cisplatin-induced acute kidney injury by attenuating endoplasmic reticulum stress-induced apoptosis via the α2AR/PI3K/AKT pathway [J].Molecular Medicine Reports,2020,21(3):1597~1605.
[10] Zhang Z,Yao L,Yang J,et al.PI3K/Akt and HIF-1 signaling pathway in hypoxia-ischemia (Review) [J].Molecular Medicine Reports,2018,18(4):3547~3554.
[11] Covington S M,Bauler L D,Toledo-pereyra L H.Akt:a therapeutic target in hepatic ischemia-reperfusion injury [J].Journal of Investigative Surgery,2017,30(1):47~55.