Liu Fu-Chao, Chaudry Irshad H, Yu Huang-Ping
*Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan †College of Medicine, Chang Gung University, Taoyuan, Taiwan ‡Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
Shock. 2017 Mar;47(3):346-351. doi: 10.1097/SHK.0000000000000736.
Corilagin, a component of Phyllanthus urinaria extract, possesses antioxidant, thrombolytic, antiatherogenic, and hepatoprotective properties, but the mechanism underlying these effects remains unclear. Previous studies showed that the Akt (protein kinase B) signaling pathway exerts anti-inflammatory and organ protective effects. The aim of this study was to investigate the mechanism of action of corilagin and determine whether these effects are mediated through the Akt-dependent pathway in a trauma-hemorrhagic shock-induced liver injury rodent model. Hemorrhagic shock was induced in male Sprague-Dawley rats; mean blood pressure was maintained at 35 mm Hg to 40 mm Hg for 90 min, followed by fluid resuscitation. During resuscitation, three doses of corilagin alone (1 mg/kg, 5 mg/kg, or 10 mg/kg, intravenously) were administered. Furthermore, a single dose of corilagin (5 mg/kg) with and without Wortmannin (1 mg/kg, PI3K inhibitor), Wortmannin alone, or vehicle was administered. Twenty-four hours after resuscitation, plasma alanine aminotransferase and aspartate aminotransferase concentration and hepatic parameters were measured. One-way ANOVA was used for statistical analysis. Hepatic myeloperoxidase activity and the concentrations of plasma alanine aminotransferase and aspartate aminotransferase, interleukin-6, tumor necrosis factor-α, intercellular adhesion molecule-1, and cytokine-induced neutrophil chemoattractant-1 (CINC-1) and CINC-3 increased following hemorrhagic shock. These parameters were significantly attenuated in corilagin-treated rats following hemorrhagic shock. Hepatic phospho-Akt expression was also higher in corilagin-treated rats than in vehicle-treated rats. The elevation of phospho-Akt was abolished by combined treatment with Wortmannin and corilagin. Our results suggest that corilagin exerts its protective effects on hemorrhagic shock-induced liver injury, at least, via the Akt-dependent pathway.
柯里拉京是叶下珠提取物的一种成分，具有抗氧化、溶栓、抗动脉粥样硬化和肝脏保护特性，但其作用机制尚不清楚。先前的研究表明，Akt（蛋白激酶B）信号通路具有抗炎和器官保护作用。本研究的目的是探讨柯里拉京的作用机制，并确定这些作用是否通过创伤性失血性休克诱导的肝损伤啮齿动物模型中的Akt依赖性途径介导。对雄性Sprague-Dawley大鼠诱导失血性休克；将平均血压维持在35 mmHg至40 mmHg 90分钟，然后进行液体复苏。在复苏过程中，单独给予三种剂量的柯里拉京（1 mg/kg、5 mg/kg或10 mg/kg，静脉注射）。此外，给予单剂量柯里拉京（5 mg/kg），同时给予或不给予渥曼青霉素（1 mg/kg，PI3K抑制剂）、单独给予渥曼青霉素或赋形剂。复苏后24小时，测量血浆丙氨酸氨基转移酶和天冬氨酸氨基转移酶浓度以及肝脏参数。采用单因素方差分析进行统计分析。失血性休克后，肝脏髓过氧化物酶活性、血浆丙氨酸氨基转移酶和天冬氨酸氨基转移酶浓度、白细胞介素-6、肿瘤坏死因子-α、细胞间黏附分子-1以及细胞因子诱导的中性粒细胞趋化因子-1（CINC-1）和CINC-3升高。在失血性休克后的柯里拉京治疗大鼠中，这些参数显著降低。柯里拉京治疗大鼠的肝脏磷酸化Akt表达也高于赋形剂治疗大鼠。渥曼青霉素和柯里拉京联合治疗可消除磷酸化Akt的升高。我们的结果表明，柯里拉京至少通过Akt依赖性途径对失血性休克诱导的肝损伤发挥保护作用。
