Clodronate-containing liposomes attenuate lung injury in rats with severe acute pancreatitis.
OBJECTIVE
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.
Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Sheng-chun
SC
Dang
De-li
DL
Jiang
Min
M
Chen
Di
D
Li
Jian-xin
JX
Zhang
D000208:Acute Disease; D000818:Animals; D004002:Clodronic Acid / Q000008:administration & dosage*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008081:Liposomes; D055370:Lung Injury / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D010195:Pancreatitis / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D008081:Liposomes; D004002:Clodronic Acid