钠氢交换蛋白1抑制剂对严重烧伤后多脏器损伤大鼠的保护作用研究

目的 探讨钠氢交换蛋白1(NHE1)抑制剂对严重烧伤后全身多脏器功能损伤大鼠的保护作用,并探讨其潜在的机制.方法 常规方法建立30%体表面积烫伤的大鼠模型.用NHE1抑制剂(卡立泊来德)干预后,通过观察组织病理学及炎症因子的改变来探讨NHE1在烧伤后多脏器损伤时所起的作用.结果 NHE1在烧伤后大量表达,而NHE1的抑制剂可显著减轻烧伤后心脏、肺脏、肾脏及小肠的损伤.同时NHE1抑制剂也可以降低肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、髓过氧化物酶(MPO)水平.结论 NHE1抑制剂显著减轻烧伤后大鼠多脏器损伤,其部分机制可能是抑制了组织的炎症反应.

Inhibition of Na+/H - exchanger 1 alleviates burn-induced multiple organ injury in rats

Objective Severe burns initiate inflammatory response characterized by the upregulation of proinflammatory cytokine , which contributes to multiple organ injury.Na+/H-exchanger 1 (NHE1) plays a significant role in several inflammatory processes.This study was designed to investigate the role of NHE1in burn-induced inflammation and multiple organ injury.Methods Rats were subjected to a 30%total body surface area full-thickness burn.Cariporide was used to assess the function of NHE1in burn-induced multiple organ injury by biochemical parameters, histologic changes, and inflammatory cytokine production.Results We found that NHE1expression was signifi-cantly increased after burn injury.Inhibition of NHE1by cariporide attenuated burn-induced edema and tissue injury in heart, lung, kidney, and small intestine.Cariporide also inhibited plasma levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and myeloperoxi-dase activity (MPO).Conclusion These results indicate that NHE1inhibition prevents burn-induced multiple organ injury.The salutary effects afforded by NHE1inhibition, at least in part, are mediated by attenuating systemic inflammatory response.