The Effect Of Mannose On Acute Pancreatitis Associated Lung Injury In Rats

Objective:Severe acute pancreatitis(SAP) is a common clinical acuteabdomen with complex complications, high mortality and poor prognosis.Acute lung injury(ALI) and Acute respiratory distress syndrome(ARDS) arethe most common and serious complications of SAP, also the main causes ofdeath. SAP often induces the systemic inflamma-tory response syndrome(SIRS) in which a large number of inflammatory chemokines and cytokinesare released and cause multiple organ dysfunction syndrome (MODS). One,slung is ofen first affected. A lot of circulating inflammatory medium infuseinto the lung tissue, activate macrophages and a large number of cytokines,such as TNF-α, IL-8, IL-l,IL-6, etc, are released by macrophages, causingthe chemotaxis and activation of PMN and lung injury.Mannose receptor (MR), as a pattern recognition receptor, is highlyexpressed in alveolar macrophages, and can recognize and combine with manypathogenic organisms, such as Candida albicans, Leishmania donovanipromastigotes,Mycobacterium tuberculosis,HIV, Pneumocystis carinii bacteriaand so on. It playes an important role in maintaining the body’s internalenvironment stable and regulate the strong inflammatory reaction in lung.There are no effective drugs with low side effects used for acutepancreatitis-associated ALI. With the development of glycobiology,anti-inflammatory effect of some carbohydrates have been found. Kossi J andhis colleagues found that mannose could alleviate the inflammation reaction ofwound healing as well as inhibit neutrophil oxidative burst and the growth ofgranulation tissue. The mannose derivatives have anti-inflammatory effect forperitonitis and adjuvant arthritis.Whether mannose inhibites the chemotaxisand activation of PMN and decreases the inflammation in the lung byinfluencing the release of inflammatory mediators in macrophages through combining with MR on macrophages is still unclear. In order to explore themechanism of the protective effect of mannose on acute pancreatitisassociated lung injury, we established this SAP associated ALI model in rats,mannose was admistrated. We observed the pathological changes in pancreasand lung, pulmonary wet／dry weight ratio, the level of pulmonary TNF-αand the expression of pulmonary MR.Methods:60healthy adult Sprague--Dawley rats(300±50g weight)wererandomly allocated into three groups：sham operation group(SO group)；severeacute pancreatitis (SAP group); mannose treatment group(MT group).Theneach group was divided into6h,12h group, as subgroups. The model wasestablished with the retrograde injection of5％sodium taurocholatesolution(1.0mL/kg) into biliopancreatic duct.The rats in the model group wasariesthetized with10％Chloral hydrate (3.0ml/kg) and given intraductalinfusion of5％sodium taurocholate solution(1.0mL/kg) at the rate of0.1ml/min after clamping the proximal end of the colnlnon bile duct andpuncturing the biliary-pancreatic duct. Sham-operated animals was operatedthe same as the SAP group, but nothing was injected. Mannose was given afteroperation in the MT group. Rats were killed at6h or12h after operation.Pacreas and right upper lobe of the lung ware fixed in4％formalin forobserving the pathology changes in them; the level of TNF-α in the lung wasexaminated by ELISA assay; the expression of pulmonary mannose receptorprotein and mRNA was examinated by immunohistochemistry staining andRT-PCR. The obtained experimental data was analyzed by statistical analysisby SPSS15.0statistical software.Results:1The pathological changes of pancreas tissue: Microscopically, thestructure of pancreatic tissue was normal in SO group; Gland interlobularsepta of the pancreas enlarged in SAP group, the structure of glandular lobulewas loose, disordered, a lot of inflammatory cells infiltrated into the interstitialpart of the pacreas, reddish edema fluid increased. In the necrotic area ofpancreas, the structure of the pacreatic acinar part disappeared, acinar cells shrinked while their nuclear soluted. As time goes on, the degree of the abovepathological changes deepened, necrotic area gradually expanded, ascitic fluidalso increased.The pathological changes in MT group were lighter than that inthe SAP group.2The pathological changes of lung tissue: Microscopically, the structureof lung tissue was generally normal in SO group; In SAP group, swellingpulmonary interstitial tissue could be seen.Wide alveolar septum,angiotelectasis hyperemia, massive infiltration of inflammatory cells and partof the alveolar space atelectasis could been found.The degree of the abovepathological changes deepened with time.The pathological changes in MTgroup was relatively lighter than that in SAP group.3Lung wet/dry weight ratio: In SO group, lung wet/dry weight ratio hadno significant difference between subgroup. Compared with SO group, lungwet/dry weight ratio was obviously higher at each time in AP group(P<0.05).Compared with SAP group, lung wet/dry weight ratio significantly reduced ineach subgroup of MT group (P<0.05).4The level of TNF-α in the lung: In SO group, there was no significantdifference between subgroups in the level of the content of TNF-α in thelung. Compared with SO group, the level of TNF-α in the lung was obviouslyhigher in each subgroup of SAP group(P<0.05). Compared with AP group, thelevel of TNF-α in the lung significantly decreased in each subgroup of MTgroup (P<0.05).5The expression of mannose receptor (MR)in the lung tissue: In SOgroup, there was no significant difference between subgroups in theexpression of mannose receptor mRNA and protein between the twosubgroup.Compared with SO group, the expression of mannose receptormRNA and protein was significantly higher at each time point in SAPgroup(P<0.05). Compared with AP group, the expression of mannose receptormRNA and protein obviously higher at each subgroup in MT group(P<0.05).Conclusion:1Mannose can reduce the damage of lung tissue in SAP rats. 2The mechanism of mannose on acute pancreatitis associated lung injurymay be upregulating the expression of mannose receptor (MR) mRNA andprotein.