| Object To study the pathogenesis of PLA2 activation in acutelung injury(ALI) secondary to severe acute pancreatitis(SAP) in rats.Toinvestigate the protective effects of a PLA2 inhibitor phosphatechloroquine(PC)in ALI secondary to SAP.Methods 54 healthy SD rats were randomly divided into threegroups, with 18 rats in each group: the sham operation(SO) group; thesevere acute pancreatitis group(SAP); the severe acute pancreatitis treatedwith phosphate chloroquine(PC) group. Rat SAP model was establishedby retrograde injection of 5% sodium taurocholate(STC) into thepancreatic duct. Phosphate chloroquine (30mg/kg) was administeredintraperitoneally ten minute later after model was established in PC group,whereas SO group and SAP group received no intervene. Rats weresacrificed at 2h, 6h, 12h after operation followed by samples collection.The PLA2 activity in the serum and lung tissue, the serum levels ofamylase, TNF-α, IL-8, total protein (TP) and total phospholipids(TPL)of the BALF were measured, meanwhile, the pathological changes ofpancreas and lungs were observed under light miscroscope, theultrastructure alteration in lung tissue were studied under TEM.Results①The PLA2 activity in the serum and lung tissue in SAPgroup were significantly higher than that in SO group(P＜0.01); Compared with SAP group, the PLA2 activity in the serum and lung tissue decreasedsignificantly in PC group(P＜0.01);②The serum level ofAMS,TNF-α,IL-8 in SAP group were significantly higher than those of SOgroup(P＜0.01). Compared with SAP group, the serum level of AMS,TNF-α,IL-8 decreased significantly in PC group(P＜0.05);③)Thecontent of total phospholipid(TPL) of BALF in SAP group decreased, andsignificantly lower than that of SO group and PC group(P＜0.01);④Thecontent of total protein (TP) of BALF in SAP group were significantlyhigher than that of SO group(P＜0.01). Compared with SAP group, thecontent of total protein decreased significantly in PC group(P＜0.01);⑤Biopsy results showed that compared with SAP group, tissue damageof lungs and pancreas were significantly relieved in PC group;⑥TEMresults showed that the structure and function of alveolar typeⅡcells inPC group were significantly better than SAP group.Conclusions The activation of PLA2 plays an important role inpathophysiological process of ALI secondary to SAP. Phosphatechloroquine can inhibit the activation of PLA2, reduce the serum level ofTNF-α, IL-6, prevent pulmonary surfactants degradation, supress someof the release of inflammatory mediators, alleviate the harm level of thepancreas and the lung, thus improve the prognosis of acute pancreatitis. |
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