Huang Yi-Shun, Liu Fu-Chao, Li Allen H, Lau Ying-Tung, Yu Huang-Ping
Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China.
Chin J Physiol. 2011 Jun 30;54(3):183-9. doi: 10.4077/cjp.2011.amm024.
Although astringinin administration under adverse circulatory conditions is known to be protective, the mechanism by which astringinin produces the salutary effects remains unknown. We hypothesize that astringinin administration in males following trauma-hemorrhage decreases cytokine production and protects against hepatic injury. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure: 40 mmHg for 90 min, then resuscitation). Different doses of astringinin (0.01, 0.03, 0.1, 0.3 mg/kg of body weight) or vehicle were administered intravenously during resuscitation. Concentrations of plasma aspartate aminotransferase (AST) with alanine aminotransferase (ALT) and various hepatic parameters were measured (n = 8 rats/group) at 24 h after resuscitation. One-way ANOVA and Tukey testing were used for statistical analysis. Trauma-hemorrhage significantly increased plasma AST and ALT levels at 24 h postresuscitation; there was a dose-related benefit when astringinin was administered at doses of 0.01 to 0.3 mg/kg. In astringinin-treated (0.3 mg/kg) rats subjected to trauma-hemorrhage, there were significant improvements in liver myeloperoxidase (MPO) activity (237.80 +/- 45.89 vs. 495.95 +/- 70.64 U/mg protein, P < 0.05), interleukin-6 (IL-6) levels (218.54 +/- 34.52 vs. 478.60 +/- 76.21 pg/mg protein, P < 0.05), cytokine-induced neutrophil chemoattractant (CINC)-1 (88.32 +/- 20.33 vs. 200.70 +/- 32.68 pg/mg protein, P < 0.05), CINC-3 (110.83 +/- 26.63 vs. 290.14 +/- 76.82 pg/mg protein, P < 0.05) and intercellular adhesion molecule (ICAM)-1 concentrations (1,868.5 +/- 211.5 vs. 3,645.0 +/- 709.2 pg/mg protein, P < 0.05), as well as in histology. Results show that astringinin significantly attenuates proinflammatory responses and hepatic injury after trauma-hemorrhage. In conclusion, the salutary effects of astringinin administration on attenuation of hepatic injury following trauma-hemorrhage are likely due to reduction of pro-inflammatory mediator levels.
尽管已知在不良循环条件下给予astringinin具有保护作用，但其产生有益作用的机制尚不清楚。我们推测，在创伤性出血后的雄性大鼠中给予astringinin可降低细胞因子的产生并预防肝损伤。雄性Sprague-Dawley大鼠经历创伤性出血（平均血压：40 mmHg，持续90分钟，然后进行复苏）。在复苏期间静脉注射不同剂量的astringinin（0.01、0.03、0.1、0.3 mg/kg体重）或赋形剂。在复苏后24小时测量血浆天冬氨酸氨基转移酶（AST）与丙氨酸氨基转移酶（ALT）的浓度以及各种肝脏参数（每组n = 8只大鼠）。采用单因素方差分析和Tukey检验进行统计分析。创伤性出血在复苏后24小时显著提高了血浆AST和ALT水平；当以0.01至0.3 mg/kg的剂量给予astringinin时存在剂量相关的益处。在接受创伤性出血的astringinin治疗组（0.3 mg/kg）大鼠中，肝脏髓过氧化物酶（MPO）活性（237.80±45.89对495.95±70.64 U/mg蛋白质，P < 0.05）、白细胞介素-6（IL-6）水平（218.54±34.52对478.60±76.21 pg/mg蛋白质，P < 0.05）、细胞因子诱导的中性粒细胞趋化因子（CINC）-1（88.32±20.33对200.70±32.68 pg/mg蛋白质，P < 0.05）、CINC-3（110.83±26.63对290.14±76.82 pg/mg蛋白质，P < 0.05）和细胞间黏附分子（ICAM）-1浓度（1,868.5±211.5对3,645.0±709.2 pg/mg蛋白质，P < 0.05）以及组织学方面均有显著改善。结果表明，astringinin可显著减轻创伤性出血后的促炎反应和肝损伤。总之，给予astringinin对减轻创伤性出血后肝损伤的有益作用可能归因于促炎介质水平的降低。
