Are gastric mucosal macrophages responsible for gastric injury in acute pancreatitis?

AIM:To investigate the protective effect of clodronatecontaining liposomes against severe acute pancreatitis(SAP)-triggered acute gastric mucosal injury(AGMI) in rats.METHODS:Clodronate- and phosphate-buffered saline(PBS)-containing liposomes were prepared by reverse-phase evaporation.The SAP rat model was established by injecting sodium taurocholate into the pancreatic subcapsular space.Sprague-Dawley rats were randomly divided into three groups:control(C),SAP plus PBS-containing liposome(P) and SAP plus clodronate-containing liposome(T).Serum tumor necrosis factor(TNF)-α levels were estimated by ELISA.Pathological changes in the gastric mucosa and pancreas were observed by hematoxylin and eosin(HE) staining.Apoptotic cells were detected by terminal deoxynucleotidyl transferase d UTP nick end labeling staining.The numbers of macrophages in the gastric mucosa were analyzed by CD68 immunohistochemical staining.RESULTS:The liposomes had a mean diameter of 150 ± 30 nm.The TNF-α levels were significantly higher in the P group than that in the C group(2 h,145.13 ± 11.50 vs 23.2 ± 2.03; 6 h,245.06 ± 12.11 vs 30.28 ± 6.07,P < 0.05),and they were significantly lower in the T group than that in the P group(2 h,93.24 ± 23.11 vs 145.13 ± 11.50; 6 h,135.18 ± 13.10 vs 245.06 ± 12.11,P < 0.05).The pathological scores of the pancreas were lower in the T group than in the P group(2 h,1.88 ± 0.83 vs 4.13 ± 0.83; 6 h,2.87 ± 0.64 vs 6.25 ± 0.88,P < 0.01).The pathological scores of the gastric mucosa were also lower in the T group than in the P group(2 h,1.12 ± 0.64 vs 2 ± 0.75; 6 h,1.58 ± 0.53 vs 3 ± 1.31,P < 0.05).In addition,increased CD68 levels were observed in the gastric mucosa of the P group compared with the C group.Clodronate-containing liposomes decreased the CD68 levels in the mucosa of the T group.The apoptotic indexes of the gastric mucosa were higher in the T group than in the P group(2 h,15.7 ± 0.92 vs 11.5 ± 1.64; 6 h,21.12 ± 1.06 vs 12.6 ± 2.44,P < 0.01).CONCLUSION:Gastric macrophages contribute to the pathogenesis of gastric injury in SAP.Clodronatecontaining liposomes have protective effects against AGMI in rats with SAP.

Clodronate-containing liposomes attenuate lung injury in rats with severe acute pancreatitis

Objectives： Severe acute pancreatitis （SAP） can lead to acute lung injury （ALl）. The purpose of this paper is to investigate the protective effect of clodronate-containing liposomes on ALl in rats with SAP. Methods： The thin film method was used to prepare liposomes. Sprague-Dawley rats were randomly divided into three groups. After the SAP model was established by injecting 5% （w/v） sodium taurocholate （2 ml/kg body weight） into the subcapsular space of the pancreata, normal saline was administered to the control （C） group, phosphate buffer solution （PBS）-containing liposome to the P group, and clodronate-containing liposome to the T group through tail veins. Blood samples were obtained from the superior mesenteric vein at 2 and 6 h to measure the levels of amylase, interleukin-6 （IL-6）, and tumor necrosis factor-a （TNF-α）. Morphological changes in the pancreata and lung were observed using hematoxylin and eosin （H＆E） staining, while cell apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL）. In addition, the macrophage marker cluster of differentiation 68 （CD68） in lung tissue was detected with immunohistochemistry. Results： Blood levels of amylase, IL-6, and TNF-α were significantly increased in the P group compared to those in the T group （P〈0.05）. In the T group, large numbers of TUNEL-positive cells were observed, but no or few in the C and P groups. Gross inspection and H＆E staining of pancreata and lung showed dramatic tissue damage, including inflammation and necrosis in the P group. Less remarkable changes were noted in the T group, and the C group exhibited normal histology. The histological scores according to Kaiser＇s criteria were consistent with H＆E findings. The number of CD68-positive macrophages decreased in the T group. Conclusions CIodronate-containing liposomes have a protective effect against ALl in rats with SAP. Blockade of macrophages may represent a novel therapeutic strategy in SAP.