Yu Huang-Ping, Hsu Jee-Ching, Hwang Tsann-Long, Yen Chia-Hung, Lau Ying-Tung
Department of Anesthesiology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
Shock. 2008 Sep;30(3):324-8. doi: 10.1097/SHK.0b013e318164f013.
Resveratrol administration after adverse circulatory conditions is known to be protective, however, the mechanism by which resveratrol produces the salutary effects remains unknown. Recently, it was shown that resveratrol activates estrogen receptor (ER) in endothelial cells. We hypothesized that resveratrol administration in males after trauma-hemorrhage decreases cytokine production and protects against hepatic injury through an ER-dependent pathway. To study this, male Sprague-Dawley rats were subjected to trauma-hemorrhage (mean blood pressure, 40 mmHg for 90 min) then resuscitation. A single dose of resveratrol (30 mg/kg of body weight) with or without an ER antagonist (ICI 182,780), ICI 182,780, or vehicle was administered i.v. during resuscitation. Tissue myeloperoxidase activity (a marker of neutrophil sequestration), cytokine-induced neutrophil chemoattractant 1 (CINC-1), CINC-3, intercellular adhesion molecule 1, and interleukin 6 (IL-6) levels in the liver and plasma aspartate aminotransferase and alanine aminotransferase concentrations were measured at 2 and 24 h postresuscitation (n = 6 rats per group). One-way ANOVA and Tukey test were used for statistical analysis. Results showed that trauma-hemorrhage increased hepatic myeloperoxidase activity, CINC-1, CINC-3, intercellular adhesion molecule 1, and IL-6 levels and plasma aspartate aminotransferase and alanine aminotransferase concentrations. These parameters were significantly improved in the resveratrol-treated rats at both 2 and 24 h postresuscitation. Coadministration of the ER antagonist ICI 182,780 prevented the beneficial effects of resveratrol administration on postresuscitation proinflammatory responses and hepatic injury. Thus, resveratrol administration after trauma-hemorrhage attenuated hepatic injury, likely through reduction of proinflammatory mediators. Resveratrol-mediated hepatic preservation seemed to progress via an ER-related pathway.
已知在不良循环条件下给予白藜芦醇具有保护作用，然而，白藜芦醇产生有益作用的机制尚不清楚。最近有研究表明，白藜芦醇可激活内皮细胞中的雌激素受体（ER）。我们推测，创伤性出血后给予雄性大鼠白藜芦醇可减少细胞因子的产生，并通过依赖ER的途径预防肝损伤。为了研究这一点，将雄性Sprague-Dawley大鼠进行创伤性出血（平均血压40 mmHg，持续90分钟），然后进行复苏。在复苏过程中，静脉注射单剂量白藜芦醇（30 mg/kg体重），同时或不给予ER拮抗剂（ICI 182,780）、ICI 182,780或赋形剂。在复苏后2小时和24小时测量肝脏组织髓过氧化物酶活性（中性粒细胞隔离的标志物）、细胞因子诱导的中性粒细胞趋化因子1（CINC-1）、CINC-3、细胞间粘附分子1以及白细胞介素6（IL-6）水平，以及血浆天冬氨酸转氨酶和丙氨酸转氨酶浓度（每组n = 6只大鼠）。采用单因素方差分析和Tukey检验进行统计分析。结果显示，创伤性出血增加了肝脏髓过氧化物酶活性、CINC-1、CINC-3、细胞间粘附分子1和IL-6水平以及血浆天冬氨酸转氨酶和丙氨酸转氨酶浓度。在复苏后2小时和24小时，白藜芦醇治疗组大鼠的这些参数均得到显著改善。同时给予ER拮抗剂ICI 182,780可阻止白藜芦醇给药对复苏后促炎反应和肝损伤的有益作用。因此，创伤性出血后给予白藜芦醇可减轻肝损伤，可能是通过减少促炎介质实现的。白藜芦醇介导的肝脏保护作用似乎是通过与ER相关的途径进行的。
