Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
PLoS One. 2013 Jun 6;8(6):e65916. doi: 10.1371/journal.pone.0065916. Print 2013.
Recent evidences show that osthole possesses anti-inflammatory properties and protective effects following shock-like states, but the mechanism of these effects remains unknown. The p38 mitogen-activated protein kinase (p38 MAPK) pathway exerts anti-inflammatory effects in injury. The aim of this study was to investigate whether p38 MAPK plays any role in the osthole-mediated attenuation of hepatic injury after trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35-40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of osthole (3 mg/kg, intravenously) with and without a p38 MAPK inhibitor SB-203580 (2 mg/kg, intravenously), SB-203580 or vehicle was administered. Plasma alanine aminotransferase (ALT) with aspartate aminotransferase (AST) concentrations and various hepatic parameters were measured (n = 8 rats/group) at 24 hours after resuscitation. The results showed that trauma-hemorrhage increased hepatic myeloperoxidase activity, intercellular adhesion molecule-1 and interleukin-6 levels, and plasma ALT and AST concentrations. These parameters were significantly improved in the osthole-treated rats subjected to trauma-hemorrhage. Osthole treatment also increased hepatic phospho-p38 MAPK expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of SB-203580 with osthole abolished the osthole-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of osthole administration on alleviation of hepatic injury after trauma-hemorrhage, which is, at least in part, through p38 MAPK-dependent pathway.
最近的证据表明，蛇床子素具有抗炎特性和对类似休克状态的保护作用，但这些作用的机制尚不清楚。p38 丝裂原活化蛋白激酶（p38 MAPK）途径在损伤中发挥抗炎作用。本研究旨在探讨 p38 MAPK 是否在创伤失血性肝损伤后蛇床子素介导的肝损伤减轻中起作用。雄性 Sprague-Dawley 大鼠接受创伤失血性休克（平均血压维持在约 35-40mmHg 90 分钟），然后进行液体复苏。在复苏过程中，单次给予蛇床子素（3mg/kg，静脉注射），并伴有或不伴有 p38 MAPK 抑制剂 SB-203580（2mg/kg，静脉注射）、SB-203580 或载体。复苏后 24 小时测量血浆丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）浓度以及各种肝参数（n=8 只/组）。结果表明，创伤失血性休克增加了肝髓过氧化物酶活性、细胞间黏附分子-1 和白细胞介素-6 水平以及血浆 ALT 和 AST 浓度。与创伤失血性休克的载体处理大鼠相比，蛇床子素处理的大鼠上述参数和肝损伤明显改善。蛇床子素处理还增加了肝磷酸化 p38 MAPK 的表达，与载体处理的创伤失血性大鼠相比。SB-203580 与蛇床子素共同给药消除了蛇床子素对上述参数和肝损伤的有益作用。这些结果表明，蛇床子素给药对创伤失血性肝损伤的保护作用至少部分是通过 p38 MAPK 依赖性途径实现的。
