摘要
目的:明确地塞米松可以减少重症急性胰腺炎(SAP)引起的肿瘤坏死因子(TNF-α)的释放,减轻TNF-α导致的肾脏血管内皮糖萼的降解,从而改善肾脏微循环和缓解肾损伤。创新点:本研究通过小鼠活体研究的方法,建立小鼠重症急性胰腺炎模型,并用地塞米松进行干预对照,采用透射电镜、激光多谱勒和酶联免疫的方法,检测了各组小鼠肾脏血管内皮糖萼的完整性、肾血流灌注和TNF-α表达情况,阐明了地塞米松对内皮糖萼的保护作用。方法:通过"胰管结扎+腹腔内雨蛙素注射"的方法建立SAP模型,分别留取各组小鼠的血液和组织标本,采用透射电镜观察内皮糖萼的损伤情况,用酶联免疫检测血清TNF-α和糖萼成份多配体聚糖的浓度,并用激光多谱勒检测活体小鼠肾脏的灌注,分析地塞米松对内皮糖萼的保护和改善肾脏灌注的作用。结论:SAP可以引起TNF-α的大量释放,并导致内皮糖萼的降解和肾脏灌注下降,而地塞米松可以减少TNF-α的释放,减轻糖萼的降解,改善肾脏血流灌注。
Objective: This study demonstrated that dexamethasone(DEX) protects the endothelial glycocalyx from damage induced by the inflammatory stimulus tumor necrosis factor-α(TNF-α) during severe acute pancreatitis(SAP), and improves the renal microcirculation. Methods: Ninety mice were evenly divided into 3 groups(Sham, SAP, and SAP+DEX). The SAP mice model was established by ligature of pancreatic duct and intraperitoneal injection of cerulein. Renal perfusion and function, and morphological changes of the glycocalyx were evaluated by laser Doppler velocimetry, electron microscopy, and histopathology(hematoxylin and eosin(H&E) staining), respectively. Serum levels of syndecan-1 and TNF-α were assessed by enzyme-linked immunosorbent assay(ELISA). The proàtectiveì effects of dexamethasone on the glycocalyx and renal microcirculation were evaluated. Results: Significantly high levels of serum TNF-α were detected 3 h after the onset of SAP. These levels might induce degradation of the glycocalyx and kidney hypoperfusion, resulting in kidney microcirculation dysfunction. The application of dexamethasone reduced the degradation of the glycocalyx and improved perfusion of kidney. Conclusions: Dexamethasone protects the endothelial glycocalyx from inflammatory degradation possibly initiated by TNF-α during SAP. This is might be a significant discovery that helps to prevent tissue edema and hypoperfusion in the future.
引文
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