丙酮酸乙酯延迟治疗通过降低大鼠血清高迁移率族蛋白B1水平减轻实验性重症急性胰腺炎。
Delayed ethyl pyruvate therapy attenuates experimental severe acute pancreatitis via reduced serum high mobility group box 1 levels in rats.
作者信息
Yang Zhi-Yong, Ling Yan, Yin Tao, Tao Jing, Xiong Jiong-Xin, Wu He-Shui, Wang Chun-You
机构信息
Department of Pancreatic Surgery, Huazhong University of Sciecne and Technology, China.
出版信息
World J Gastroenterol. 2008 Jul 28;14(28):4546-50. doi: 10.3748/wjg.14.4546.
AIM
To investigate the effect of delayed ethyl pyruvate (EP) delivery on distant organ injury, survival time and serum high mobility group box 1 (HMGB1) levels in rats with experimental severe acute pancreatitis (SAP).
METHODS
A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups (n = 32 in each group): sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP (30 mg/kg) at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) levels were measured. Lung wet-to-dry-weight (W/D) ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats.
RESULTS
Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios (8.22 +/- 0.42 vs 9.76 +/- 0.45, P < 0.01), pulmonary histological scores (7.1 +/- 0.7 vs 8.4 +/- 1.1, P < 0.01), serum AST (667 +/- 103 vs 1 368 +/- 271, P < 0.01), ALT (446 +/- 91 vs 653 +/- 98, P < 0.01) and Cr (1.2 +/- 0.3 vs 1.8 +/- 0.3, P < 0.01) levels. SAP rats had a median survival time of 44 h. Delayed EP treatment significantly prolonged median survival time to 72 h (P < 0.01).
CONCLUSION
Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGB1levels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome (MODS) in SAP patients.
目的
探讨延迟给予丙酮酸乙酯（EP）对实验性重症急性胰腺炎（SAP）大鼠远隔器官损伤、生存时间及血清高迁移率族蛋白B1（HMGB1）水平的影响。
方法
通过向大鼠胰管逆行注射人工胆汁诱导建立SAP模型。将动物随机分为三组（每组n = 32）：假手术组、SAP组和延迟EP治疗组。延迟EP治疗组大鼠在诱导SAP后12 h、18 h和30 h给予EP（30 mg/kg）。在诱导SAP后24 h和48 h处死动物并取材。检测血清HMGB1、天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、血尿素氮（BUN）和肌酐（Cr）水平。计算肺湿干重（W/D）比值和组织学评分以评估肺损伤。在SAP组和延迟EP治疗组之间进行额外实验，研究EP对SAP大鼠生存时间的影响。
结果
延迟EP治疗显著降低血清HMGB1水平，并减轻肝、肾和肺损伤，肺W/D比值降低（8.22±0.42对9.76±0.45，P < 0.01），肺组织学评分降低（7.1±0.7对8.4±1.1，P < 0.01），血清AST（667±103对1368±271，P < 0.01）、ALT（446±91对653±98，P < 0.01）和Cr（1.2±0.3对1.8±0.3，P < 0.01）水平降低。SAP大鼠的中位生存时间为44 h。延迟EP治疗显著延长中位生存时间至72 h（P < 0.01）。
结论
延迟EP治疗可减轻实验性SAP大鼠的远隔器官损伤并延长生存时间，其机制可能是降低血清HMGB1水平。EP可能成为治疗SAP患者炎症反应和多器官功能障碍综合征（MODS）的有效新疗法。
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