title: The hydrocortisone protection of glycocalyx on the intestinal capillary endothelium during severe acute pancreatitis.
abstract: Malfunctioning of the intestinal microcirculation secondary to severe acute pancreatitis (SAP) can cause injuries to the intestinal mucosal barrier, translocation of gut flora, and sepsis. The glycocalyx on the vascular endothelium helps maintain its normal function through multiple mechanisms, including regulation of vascular permeability and inhibition of intercellular adhesion. It is unknown that whether pancreatitis inflicts injuries to the intestinal mucosal barrier through damaging glycocalyx or stabilizing glycocalyx can be a potential therapeutic target in maintaining the integrity of the intestinal mucosal barrier during SAP. Injecting sodium taurocholate into the pancreatic duct of Sprague-Dawley rats induced SAP. Intestinal perfusion, changes in endothelial glycocalyx, and the associated molecular mechanisms were assessed by laser Doppler velocimetry, electron microscopy, and the levels of heparan sulfate, syndacan-1, and tumor necrosis factor-α (TNF-α) in the superior mesenteric vein. Protective effects of hydrocortisone treatment in the intestinal microcirculation during SAP were evaluated. Degradation of the glycocalyx in intestinal vascular endothelium developed 3 h after the onset of SAP in rats. By 12 h, significant reduction of intestinal perfusion was observed. The concomitant elevated levels of TNF-α in the superior mesenteric vein suggest that TNF-α is involved in the degradation of the glycocalyx. With the use of hydrocortisone, intestinal perfusion was improved and the degradation of glycocalyx was reduced. The degradation of glycocalyx is involved in the malfunction of the intestinal microcirculation. The massive release of TNF-α participates in this process and leads to glycocalyx degradation. Hydrocortisone may be a good therapy to prevent this process.
authors.affiliation: *The Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, and †The Women's Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Shun-Liang
authors.initials: SL
authors.lastname: Gao
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shao-Yang
authors.initials: SY
authors.lastname: Zhang
authors.forename: Zhong-Yan
authors.initials: ZY
authors.lastname: Liang
authors.forename: Wen-Qiao
authors.initials: WQ
authors.lastname: Yu
authors.forename: Ting-Bo
authors.initials: TB
authors.lastname: Liang
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism*; D019276:Glycocalyx / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism; D006854:Hydrocortisone / Q000737:chemistry*; D007422:Intestines / Q000187:drug effects; D008297:Male; D008642:Mesenteric Veins / Q000378:metabolism; D008833:Microcirculation; D010195:Pancreatitis / Q000378:metabolism*; D010477:Perfusion; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000382:microbiology; D053668:Syndecan-1 / Q000378:metabolism; D013656:Taurocholic Acid / Q000008:administration & dosage; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D006497:Heparan Sulfate; D006854:Hydrocortisone; D053668:Syndecan-1; D013656:Taurocholic Acid; D014409:Tumor Necrosis Factor-alpha; C508243:Sdc1 protein, rat