Department of Emergency Medicine, Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China,
Inflamm Res. 2014 Aug;63(8):675-82. doi: 10.1007/s00011-014-0740-6. Epub 2014 May 20.
Previous studies indicate that endotoxin preconditioning may decrease the inflammatory response and alleviate intestinal mucosal damage caused by sepsis. However, it is not known whether preconditioning with endotoxin might protect the intestinal mucosa after hemorrhagic shock. In this study, we investigated the effect of lipopolysaccharide (LPS) preconditioning on the intestinal mucosa following hemorrhagic shock in a rat model. Given that intestinal toll-like receptor 4 (TLR4) signaling is exaggerated in response to LPS, we further investigated the role of TLR4 signaling in endotoxin tolerance.
Animals were pre-treated with intra-peritoneal Escherichia coli LPS for 5 days prior to hemorrhagic shock. Animals were bled to achieve a mean arterial pressure (MAP) of 35-40 mmHg, then resuscitated with Ringer solution and the heparinized shed blood to maintain MAP between 90 and 100 mmHg. The distal ileum was harvested after resuscitation and graded for mucosal damage. TNF-α, TLR4, cleaved caspase-3, and intestinal trefoil factor 3 (TFF3) levels were measured at different time points.
Pretreatment with LPS significantly reduced intestinal mucosal damage and protein levels of cleaved caspase-3. Furthermore, animals pre-treated with LPS experienced reduction of TNF-α and increased mucosal expression of TFF3. LPS tolerance was associated with reduced TLR4 expression.
Endotoxin preconditioning can lessen the effects of ischemia and reperfusion injury in intestinal mucosa of a rat model with hemorrhagic shock. It is hypothesized that this effect is mediated via inhibition of TLR4 over-expression.
先前的研究表明，内毒素预处理可能会减轻脓毒症引起的炎症反应并减轻肠道黏膜损伤。然而，目前尚不清楚内毒素预处理是否可以在出血性休克后保护肠道黏膜。在这项研究中，我们研究了脂多糖（LPS）预处理对出血性休克大鼠模型肠道黏膜的影响。鉴于肠道 Toll 样受体 4（TLR4）信号在 LPS 作用下被夸大，我们进一步研究了 TLR4 信号在内毒素耐受中的作用。
动物在出血性休克前通过腹腔内大肠杆菌 LPS 预处理 5 天。将动物放血至平均动脉压（MAP）为 35-40mmHg，然后用林格氏液和肝素化的失血进行复苏，以维持 MAP 在 90-100mmHg 之间。复苏后采集回肠远端并进行黏膜损伤分级。在不同时间点测量 TNF-α、TLR4、裂解 caspase-3 和肠三叶因子 3（TFF3）的水平。
LPS 预处理可显著减轻肠道黏膜损伤和裂解 caspase-3 的蛋白水平。此外，LPS 预处理的动物 TNF-α减少，黏膜 TFF3 表达增加。内毒素耐受与 TLR4 表达减少有关。
内毒素预处理可以减轻出血性休克大鼠模型肠道黏膜缺血再灌注损伤的影响。据推测，这种作用是通过抑制 TLR4 过表达介导的。
