The role of tumour necrosis factor‐α in renal dysfunction following mild haemorrhage in rats
The role of tumour necrosis factor‐α in renal dysfunction following mild haemorrhage in rats
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肿瘤坏死因子-α在大鼠轻度出血肾功能障碍中的作用
DOI：
10.1111/j.0959-9673.2004.00403.x
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发表时间：
2004
影响因子：
3
通讯作者：
N. Tanaka
中科院分区：
文献类型：
--
作者：
Hiroaki Sato;Toshiko Tanaka;T. Kita;Hiroki Yamaguchi;N. Tanaka
轻度出血偶尔会导致肾脏或多个器官衰竭后的延迟性死亡，但确切的机制尚未确定。我们研究了肿瘤坏死因子-α(肿瘤坏死因子-α)在轻度出血所致肾损害中的作用。肿瘤坏死因子是一种主要的促炎细胞因子，可导致多器官衰竭。雄性麻醉大鼠经颈总动脉导管放血20 m in，放血总量16.7%，出血量1.09 m l/100 g体重，无液体复苏，可致轻度出血。平均动脉压和心率在出血后即刻下降，但在出血后5 h恢复到基线水平。肾组织肿瘤坏死因子α基因表达和血清肿瘤坏死因子α水平均以出血后1 h最高。腹腔注射肿瘤坏死因子α的抑制物FR167653和白细胞介素1β可显著抑制肿瘤坏死因子α的升高。FR167653可抑制出血所致的炎症细胞浸润和肾小管上皮细胞损伤，显著改善肾功能障碍。治疗组的形态学改变也比未治疗组的小。据报道，肿瘤坏死因子-α对中性粒细胞IL-1β的释放和激活有显著影响，并在其他促炎细胞因子的表达中发挥关键作用。我们的数据显示，内源性肿瘤坏死因子-α确实在轻度出血时肾功能障碍中起关键作用。这些结果将有助于法医病理学家解释轻度出血引起的肾功能障碍的发病机制，并确定轻度出血后无明显形态变化的死亡原因。
Mild haemorrhage occasionally causes delayed death following failure of kidney or multiple organs, but the precise mechanisms have not yet been identified. We investigated the role of tumour necrosis factor‐α (TNF‐α), known as a major pro‐inflammatory cytokine that leads to multiple organ failure, on the renal damage induced by mild haemorrhage. A mild haemorrhagic state was induced in male anaesthetized rats by bleeding via a common carotid catheter for 20 min at 16.7% of total body blood, 1.09 ml/100 g body weight, without fluid resuscitation. Mean arterial pressure and heart rate decreased soon after haemorrhaging but returned to baseline level up to 5 h after bleeding. TNF‐α mRNA expression in the kidney and serum TNF‐α levels were highest at 1 h after bleeding. Intraperitoneal pretreatment with FR167653, an inhibitory compound of TNF‐α production, as well as of interleukin (IL)‐1β, significantly inhibited the increase in TNF‐α. The inflammatory cell infiltration and tubular cell injury induced by haemorrhage were suppressed, and the renal dysfunction was dramatically improved by the FR167653 treatment. The morphological changes were also less in the treated group than in those that had not been treated. TNF‐α has been reported to have striking effects on IL‐1β release and activation of neutrophils, and to play a pivotal role in the expression of the other pro‐inflammatory cytokines. Our data show that endogenously‐derived TNF‐α does play a key role in the renal dysfunction during mild haemorrhage. These results should be useful to forensic pathologists to explain the pathogenesis of renal dysfunction induced by a mild haemorrhage and to identify the cause of death where there are no significant morphological changes after mild haemorrhage.
影响因子：
15.9
作者：
Takada, M;Nadeau, KC;Tilney, NL
通讯作者：
Tilney, NL