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丙泊酚对大鼠肝缺血再灌注损伤的作用及机制。

Effect and mechanism of propofol in hepatic ischemia/reperfusion injury of rat.

机构信息

Department of Anesthesiology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Aug;21(15):3516-3522.

PMID:28829487
Abstract

OBJECTIVE

Hepatic ischemia/reperfusion (I/R) injury remains to be one of the most common clinical diseases. This study aimed to explore the potential effect and mechanism of propofol in protecting rat liver from I/R injury.

MATERIALS AND METHODS

The hepatic I/R model was established in Sprague-Dawley (SD) rats by perfusing the liver with heparinized cold saline through the portal vein for 20 min. The rats were then received a 100 mg/kg/d propofol administration for the continuously 10 days. The hepatic function indexes of ALT, AST, and GGT were detected by ELISA. The apoptosis of hepatic cells was assessed by TUNEL analysis, and Bax and Bcl-2 expression changes were detected by qRT-PCR and Western blotting. In addition, serum pro-inflammatory factors and the signaling pathway-related protein expressions were detected.

RESULTS

Propofol markedly attenuated the increases of ALT, AST, and GGT induced by I/R. Propofol reduced I/R-induced apoptosis and pro-inflammatory factors secretion. Furthermore, propofol could promote the expression of phosphorylated (p)-AKT and inhibited the expression of p-mTOR.

CONCLUSIONS

Propofol protects hepatic I/R injury partly by reducing apoptosis and reducing the release of pro-inflammatory cytokines, which is possibly involved in the modulation of the PI3K/AKT/mTOR signaling pathway. All these data suggest that propofol may play certain positive roles in protecting the liver from I/R injury.

摘要

目的

肝缺血/再灌注(I/R)损伤仍然是最常见的临床疾病之一。本研究旨在探讨异丙酚在保护大鼠肝 I/R 损伤中的潜在作用和机制。

材料和方法

通过门静脉向肝素化冷盐水中灌注 20 分钟,在 Sprague-Dawley(SD)大鼠中建立肝 I/R 模型。然后,大鼠连续 10 天接受 100mg/kg/d 异丙酚给药。通过 ELISA 检测丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和γ-谷氨酰转移酶(GGT)等肝功能指标。通过 TUNEL 分析评估肝细胞核的凋亡情况,并通过 qRT-PCR 和 Western blot 检测 Bax 和 Bcl-2 表达变化。此外,检测血清促炎因子和信号通路相关蛋白的表达。

结果

异丙酚显著降低 I/R 引起的 ALT、AST 和 GGT 升高。异丙酚减少 I/R 诱导的细胞凋亡和促炎因子分泌。此外,异丙酚可以促进磷酸化(p)-AKT 的表达,抑制 p-mTOR 的表达。

结论

异丙酚通过减少细胞凋亡和减少促炎细胞因子的释放来部分保护肝 I/R 损伤,这可能涉及到 PI3K/AKT/mTOR 信号通路的调节。所有这些数据表明,异丙酚可能在保护肝脏免受 I/R 损伤方面发挥一定的积极作用。

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