| Background and objective:Obstructive jaundice as a common clinical pathological state, is involving calculus ofbile duct, bile duct and pancreatic cancer and various diseases on the cause. By resection oflesions, biliary drainage of bile and reduction of bile duct pressure, surgery is the maintreatment for obstructive jaundice. Although supported by a strong application of antibiotics,a variety of infections, sepsis, and multiple organ failure, are still the leading causes ofcommon complications and death in patients with obstructive jaundice during theperioperative period. Various clinical and experimental studies have shown that, intestinalmucosal barrier damage, increased intestinal permeability is an important factor leading tosepsis and multiple organ failure under obstructive jaundice state. Therefore, to research theeffective prevention and treatment of intestinal mucosal barrier damage, and to explore itsmechanisms have an important clinical significance for obstructive jaundice.Adrenomedullin (AM), as a vasoactive peptide, was originally isolated from humanpheochromocytoma tissue in1993, and it has a widely distribution in variety of tissues andorgans. As a biologically active peptide, AM has a wide range of physiological effects,including vasodilatory and hypotensive properties, regulation of salt and water metabolism,apoptosis suppression and other functions. Via combining with adhesion molecules on thecell surface, adrenomedullin binding protein-1(AMBP-1) can promote AM binding to itsreceptor, and potentiates AM biological activities. Research shows that intravenous infusionof AM/AMBP-1can ameliorates sepsis-induced organ injury and systemic inflammatoryresponse in jaundiced rats, but the exact pathophysiological mechanism is still unclear. Wespeculate that the supplement of AM/AMBP-1, can improve the intestinal mucosal barrierfunction in obstructive jaundice, thus reduced the incidence of systemic inflammatoryresponse and sepsis. The aim of this study is, therefore, to observe the protective effect ofAM and AMBP-1on intestinal mucosal barrier in a rat model of obstructive jaundice, inorder to provide a new theoretical basis and strategies for the prevention and treatment of obstructive jaundice secondary to gut derived sepsis.Materials and methods:48male Sprague-Dawley rats were randomly divided into Sham group, obstructivejaundice vehicle control group and AM/AMBP-1treatment group. Obstructive jaundice wasinduced in adult rats by common bile duct ligation (CBDL).6days after CBDL, the ratswere administered with AM/AMBP-1(24/80μg/kg BW) or vehicle (i.e. human albumin)through femoral vein. Blood and tissue samples were collected at24h after administeredAM/AMBP-1for various measurements. The intestinal permeability was assessed bymonitoring plasma concentrations of the fluorescein isothiocyanate-dextran (FITC-D)after its injection into the ileum. DXC800automatic biochemical analyzer was used for thedetermination of serum concentrations of aspartate aminotransferase (AST), alanineaminotransferase (ALT) and total bilirubin (TBIL). Serum level of TNF-α was measured byenzyme-linked immunosorbent assay. The apoptosis of intestinal cells was detected byterminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Theexpression of cleaved caspase-3was measured by western blotting. Morphologicalchanges in the small intestine were assessed by HE staining.Results:Compared with the Sham group, the intestinal permeability increased remarkably (P<0.05), and the serum levels of TBIL, ALT, AST and TNF-α increased obviously in theVehicle control group and the AM/AMBP-1group (P <0.05). Meanwhile, the intestinalexpression of cleaved caspase-3, the apoptosis index (AI) and Chiu’s score weresignificantly increased in the Vehicle control group and the AM/AMBP-1group (P <0.05).Compared with the Vehicle control group, the development of intestinalhyperpermeability was significantly attenuated (P <0.05), and the serum levels of TNF-αdecreased obviously in the AM/AMBP-1group (P <0.05). The expression of cleavedcaspase-3, the AI and Chiu’s score were significantly decreased in the AM/AMBP-1group(P <0.05). However, there is no significant difference in the serum levels of TBIL, ALT andAST between the Vehicle control group and the AM/AMBP-1group.Conclusions:Supplementary AMBP-1can significantly attenuate the development of intestinalhyperpermeability, and ameliorate intestinal barrier function in obstructive jaundice.Supplementary AM/AMBP-1can maintain and protect the intestinal mucosal barrier function by inhibiting apoptosis of intestinal tissue.Supplementary AM/AMBP-1significantly reduces serum TNF-α in obstructivejaundice rats, and mitigates the systemic inflammatory response. |
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