Wang Houhong, Tang A-Mao, Liu Daren, Li Guogang, Ye Longyun, Li Xiaowen, Li Chao, Chen Li
Department of Surgery, Zhejiang University School of Medicine, Second Affiliated Hospital, Hangzhou, Zhejiang 310009;
Exp Ther Med. 2013 Jul;6(1):29-32. doi: 10.3892/etm.2013.1075. Epub 2013 Apr 24.
Acute pancreatitis, affecting 382,014 individuals annually in China, is life-threatening in its severe form. Since acute pancreatitis-associated morbidity or mortality is attributable mainly to functional failure of the vital organs, significant research efforts have focused on the identification of novel agents with potential organ-protective properties in the hope of developing approaches to improve the outcome of acute pancreatitis. In a previous study, we demonstrated that sivelestat, a specific inhibitor of neutrophil elastase (NE), is effective in protecting against lung failure in rats with taurocholate-induced acute pancreatitis. As part of the analyses extended from that study, the present study aimed to evaluate the role of sivelestat in the protection against acute pancreatitis-associated renal injury. Renal histopathology and major renal function parameters were analyzed in renal tissue and blood specimens collected from rats with acute pancreatitis induced by the surgical administration of sodium taurocholate in the presence or absence of sivelestat treatment and in sham-operated control rats at various time-points. The extended analyses demonstrated that: i) sodium taurocholate induced apparent renal injury and dysfunction manifested by histological anomalies, including vacuolization and apoptosis of the cells of the tubular epithelial lining in the kidney, as well as biochemical aberrations in the blood (increases in levels of blood urea nitrogen, creatinine and tumor necrosis factor-α) and renal tissue (robust increases in NE activity and induced neutrophil chemoattractant-1 levels); and ii) sivelestat treatment effectively attenuated all taurocholate-induced histological anomalies and biochemical aberrations. These observations strongly suggest that the NE inhibitor, sivelestat, is effective in protecting against acute pancreatitis-associated renal injury.
急性胰腺炎在中国每年影响382,014人，其严重形式会危及生命。由于急性胰腺炎相关的发病率或死亡率主要归因于重要器官的功能衰竭，大量研究致力于寻找具有潜在器官保护特性的新型药物，以期开发改善急性胰腺炎预后的方法。在之前的一项研究中，我们证明了西维来司他（一种中性粒细胞弹性蛋白酶（NE）的特异性抑制剂）对牛磺胆酸钠诱导的急性胰腺炎大鼠的肺功能衰竭具有保护作用。作为该研究扩展分析的一部分，本研究旨在评估西维来司他在预防急性胰腺炎相关肾损伤中的作用。在不同时间点，从接受或未接受西维来司他治疗的牛磺胆酸钠手术诱导的急性胰腺炎大鼠以及假手术对照大鼠收集的肾组织和血液标本中，分析肾脏组织病理学和主要肾功能参数。扩展分析表明：i）牛磺胆酸钠诱导明显的肾损伤和功能障碍，表现为组织学异常，包括肾近端小管上皮细胞空泡化和凋亡，以及血液（血尿素氮、肌酐和肿瘤坏死因子-α水平升高）和肾组织（NE活性显著增加以及诱导中性粒细胞趋化因子-1水平升高）中的生化异常；ii）西维来司他治疗有效减轻了所有牛磺胆酸钠诱导的组织学异常和生化异常。这些观察结果强烈表明，NE抑制剂西维来司他对预防急性胰腺炎相关肾损伤有效。
