Wang Qiang, Yao Yong-ming, Wang Yan-bo, Wang Wen-jiang, Xian Li-ming, Dou Ke-feng, Sheng Zhi-yong
Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Zhonghua Wai Ke Za Zhi. 2007 Sep 1;45(17):1210-3.
To investigate the effect of ethyl pyruvate (EP) on high mobility group box-1 protein (HMGB1) expression in renal tissue and acute kidney injury in rats with delayed resuscitation after thermal injury.
Seventy-eight Wistar rats subjected to 30% total body surface area full-thickness thermal injury followed with delayed resuscitation were divided into 3 groups: sham group (n = 18), injury group (n = 30) and EP group (n = 30). Renal tissue and blood samples were harvested to determine HMGB1 mRNA as well as its protein expression and renal function parameter at the 8, 24, 72 h post the "injury". HMGB1 mRNA was semi-quantitatively measured by reverse transcription polymerase chain reaction taking GAPDH as an internal standard, and HMGB1 protein expression was determined by Western blot and immunohistochemistry. Blood urea nitrogen (BUN) levels were measured with automatic biochemistry analyzer. The pathological changes of renal tissues were examined using HE staining.
Compared with sham controls, both mRNA and protein expressions of HMGB1 in injury group were significantly enhanced in kidneys at 8 - 72 h after thermal injury (P < 0.05), meanwhile serum BUN levels were markedly increased (P < 0.05). Compared with injury group, the renal HMGB1 mRNA and protein expressions were markedly down-regulated in EP group at 8 h, 24 h and 72 h post injury (P < 0.05), respectively, and meanwhile serum BUN levels were reduced significantly (P < 0.05). Inflammatory cell infiltration was found in renal tissues following injury, and kidney injury was markedly alleviated after treatment with EP.
It indicated that HMGB1 appears to be involved in the pathogenesis of post-burn acute kidney injury. Treatment with EP reduces renal HMGB1 expression, and protects against acute kidney injury secondary to delayed resuscitation after major burns.
探讨丙酮酸乙酯（EP）对热损伤延迟复苏大鼠肾组织中高迁移率族蛋白B1（HMGB1）表达及急性肾损伤的影响。
将78只体表面积30%全层热损伤后延迟复苏的Wistar大鼠分为3组：假手术组（n = 18）、损伤组（n = 30）和EP组（n = 30）。于“损伤”后8、24、72 h采集肾组织和血样，检测HMGB1 mRNA及其蛋白表达和肾功能指标。以GAPDH为内参，采用逆转录聚合酶链反应半定量检测HMGB1 mRNA，采用蛋白质印迹法和免疫组织化学法检测HMGB1蛋白表达。用自动生化分析仪检测血尿素氮（BUN）水平。采用苏木精-伊红（HE）染色观察肾组织病理变化。
与假手术对照组相比，热损伤后8 - 72 h损伤组肾脏中HMGB1的mRNA和蛋白表达均显著增强（P < 0.05），同时血清BUN水平明显升高（P < 0.05）。与损伤组相比，EP组在损伤后8 h、24 h和72 h时肾组织中HMGB1的mRNA和蛋白表达均明显下调（P < 0.05），同时血清BUN水平显著降低（P < 0.05）。损伤后肾组织出现炎性细胞浸润，EP治疗后肾损伤明显减轻。
表明HMGB1可能参与烧伤后急性肾损伤的发病机制。EP治疗可降低肾组织中HMGB1表达，对重度烧伤延迟复苏继发的急性肾损伤具有保护作用。
