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

摘要

Objectives: Severe acute pancreatitis (SAP) can lead to acute lung injury (ALI). The purpose of this paper is to investigate the protective effect of clodronate-containing liposomes on ALI 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-α (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: Clodronate-containing liposomes have a protective effect against ALI in rats with SAP. Blockade of macrophages may represent a novel therapeutic strategy in SAP.