N(2)-L-丙氨酰-L-谷氨酰胺抑制失血性休克大鼠肠黏膜损伤

N(2)-L-alanyl-L-glutamine inhibits intestinal mucosal injury in hemorrhagic shock rats

目的探讨N(2)-L-丙氨酰-L-谷氨酰胺(NLAG)对失血性休克大鼠肠黏膜屏障的作用及其对TLR4/Myd88信号通路表达的影响。方法清洁级SD大鼠30只,随机分为假手术组(Sham)、失血性休克组(HS)和NLAG组,每组10只。按大鼠总血容量35%放血建立HS模型,HS组自体血回输复苏,NLAG组于HS后腹腔注射NLAG。于HS发生后4h处死大鼠,观察小肠组织病理学结果;检测血中肠脂肪酸结合蛋白(I-FABP)和D-乳酸浓度;ELISA检测血清中TNF-α、IL-6、IL-10浓度;Western-blot法检测TLR4、Myd88、NF-κB蛋白表达水平。结果 NLAG抑制脓毒症引发的全身炎症反应,降低血浆中I-FABP、D-乳酸含量,下调血浆中TNF-,IL-6和IL-10含量;抑制肠损伤,改善肠屏障功能,降低肠粘膜TLR4、Myd88、NF-κB蛋白表达水平。结论

Objective To investigate the inhibitory effect of N （2） -L-alanyl-L- glutamine（NLAG） on intestinal mucosal injury in rats with hemorrhagic shock. Methods 30 SD rats were randomly divided into sham group（Sham）, hemorrhagic shock group（HS） and N （2） -L- alanyl -L- glutamine group（NLAG）. The pathological chang was observed by HE staining, blood intestinal fatty acid binding protein （I-FABP） and D- ELISA were determined, concentrations of TNF-, IL-6, IL alpha -10 in serum were detected by ELISA, TLR4, Myd88, NF- kappa B protein expressions in intestinal mucus were detected by Western-blot. Results NLAG inhibited the systemic inflammatory response induced by sepsis, inhibited intestinal injury, improved intestinal barrier function, reduced plasma I-FABP, D- lactic acid concentrations, downregulated concentrations of TNF-, IL-6 and IL-10 in rat plasma and expression levels of TLR4, Myd88, NF- kappa B in intestinal mucus. Conclusion The inhibition of NLAG on the intestinal mucosal injury of HS ratsmight be related to the decrease of inflammation factors and TLR4/Myd88 signaling pathway.