Effects of Mesalamine Treatment on Gut Barrier Integrity After Burn Injury.
Effects of Mesalamine Treatment on Gut Barrier Integrity After Burn Injury.
复制标题
DOI：
10.1097/bcr.0000000000000396
复制
发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Choudhry MA
中科院分区：
文献类型：
--
作者：
Cannon AR;Akhtar S;Hammer AM;Morris NL;Javorski MJ;Li X;Kennedy RH;Gamelli RL;Choudhry MA
肠道屏障破坏通常与烧伤和其他创伤相关的发病机制有关。在这项研究中，我们研究了美沙拉嗪 (5-ASA)（一种炎症性肠病患者的常见抗炎治疗方法）的治疗干预是否可以减少烧伤后肠道炎症并维持正常的屏障完整性。对雄性 C57BL/6 小鼠进行约 20% 全身表面积的背部烫伤，并用 1mL 生理盐水或溶解在盐水中的 100mg/kg 5-ASA 进行复苏。我们在烧伤后一天，在存在或不存在 5-ASA 的情况下检查了肠道转运和通透性，以及小肠上皮细胞促炎细胞因子的水平和紧密连接蛋白的表达。烧伤后一天观察到肠道转运显着减少，同时肠道通透性显着增加。我们发现损伤一天后小肠上皮细胞中 IL-6（约 1.5 倍）和 IL-18（约 2.5 倍）的水平大幅增加。此外，烧伤会降低紧密连接蛋白claudin-4、claudin-8和occludin的表达。烧伤后用 5-ASA 治疗可防止烧伤引起的通透性增加，部分恢复正常肠道转运，使促炎细胞因子 IL-6 和 IL-18 水平正常化，并将 Claudin-4 和 Occludin 紧密连接蛋白表达恢复至假手术水平。这些研究结果表明，5-ASA 有可能用于治疗烧伤后减少肠道炎症并使肠道功能正常化。
Gut barrier disruption is often implicated in pathogenesis associated with burn and other traumatic injuries. In this study, we examined whether therapeutic intervention with mesalamine (5-ASA), a common anti-inflammatory treatment for patients with inflammatory bowel disease, reduces intestinal inflammation and maintains normal barrier integrity after burn injury. Male C57BL/6 mice were administered an ~20% total body surface area dorsal scald burn and resuscitated with either 1mL normal saline or 100mg/kg of 5-ASA dissolved in saline. We examined intestinal transit and permeability along with levels of small intestine epithelial cell pro-inflammatory cytokines and tight junction protein expression one day after burn injury in the presence or absence of 5-ASA. A significant decrease in intestinal transit was observed one day after burn injury, which accompanied a significant increase in gut permeability. We found a substantial increase in the levels of IL-6 (by ~1.5 fold) and IL-18 (by ~2.5 fold) in small intestine epithelial cells one day after injury. Furthermore, burn injury decreases expression of the tight junction proteins claudin-4, claudin-8, and occludin. Treatment with 5-ASA after burn injury prevented the burn induced increase in permeability, partially restored normal intestinal transit, normalized levels of the pro-inflammatory cytokines IL-6 and IL-18, and restored tight junction protein expression of claudin-4 and occludin to that of sham levels. Together these findings suggest that 5-ASA can potentially be used as treatment to decrease intestinal inflammation and normalize intestinal function after burn injury.