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通过调节 Cyp2b10/Cyp3a25 通路来保护丙泊酚对肝缺血再灌注损伤。

Protection of propofol on liver ischemia reperfusion injury by regulating Cyp2b10/ Cyp3a25 pathway.

机构信息

Department of General Surgery, the Second Affiliated Hospital of Soochow University, Suzhou 215000, China; Department of Anesthesiology, the Affiliated Hospital of Guizhou Medical University, Guiyang 550000, China.

Department of Hepatobiliary Surgery, the Affiliated Hospital of Guizhou Medical University, Guiyang 550000, China.

出版信息

Tissue Cell. 2022 Oct;78:101891. doi: 10.1016/j.tice.2022.101891. Epub 2022 Aug 6.

Abstract

To verify whether propofol alleviates liver ischemia-reperfusion injury (IRI) in mice by regulating Cyp2b10/ Cyp3a25 pathway. The liver I/R injury in vivo and in vitro model was constructed. The serum level of AST, ALT, ALP and ALB was detected using ELISA. The mRNA and protein expression of Cyp2b10 and Cyp3a25 were determined by qRT-PCR and western blot, respectively. The liver cell activity was assessed by MTT assay. The binding between Cyp2b10 and Cyp3a25 was evaluated by online website prediction, CoIP, and cell transfection with Cyp2b10 siRNA and pcDNA3.1-Cyp3a25. The hepatocyte apoptosis was examined using flow cytometry assay. The serum level of AST, ALT, ALP was increased and that of ALB was decreased in liver I/R injury in vivo model. Also, the mRNA and protein expression of Cyp2b10 and Cyp3a25 were enhanced and reduced in liver I/R injury in vivo and vitro model respectively. The liver cell activity was markedly reduced in H/R cell model. However, these changes were all reversed with propofol treatment. Furthermore, Cyp2b10 could directly bind to Cyp3a25 to regulate the H/R-induced hepatocyte apoptosis. Propofol plays an effect of on liver I/R injury by regulating Cyp2b10/ Cyp3a25 pathway.

摘要

为了验证异丙酚是否通过调节 Cyp2b10/Cyp3a25 通路来减轻小鼠肝缺血再灌注损伤(IRI)。构建了体内和体外肝 I/R 损伤模型。使用 ELISA 检测血清中天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)和白蛋白(ALB)的水平。通过 qRT-PCR 和 Western blot 分别测定 Cyp2b10 和 Cyp3a25 的 mRNA 和蛋白表达。通过 MTT 测定评估肝细胞活性。通过在线网站预测、CoIP 和 Cyp2b10 siRNA 和 pcDNA3.1-Cyp3a25 的细胞转染评估 Cyp2b10 和 Cyp3a25 之间的结合。通过流式细胞术检测肝细胞凋亡。在体内肝 I/R 损伤模型中,血清 AST、ALT、ALP 水平升高,ALB 水平降低。此外,Cyp2b10 和 Cyp3a25 的 mRNA 和蛋白表达分别在体内和体外肝 I/R 损伤模型中增强和减少。在 H/R 细胞模型中,肝细胞活性明显降低。然而,这些变化都随着异丙酚治疗而逆转。此外,Cyp2b10 可以直接与 Cyp3a25 结合,调节 H/R 诱导的肝细胞凋亡。异丙酚通过调节 Cyp2b10/Cyp3a25 通路发挥对肝 I/R 损伤的作用。

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