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

• Published in: Journal of Zhejiang University. B. Science 2010-11, Vol.11 (11), p.828-835
• Main Authors: Dang, Sheng-chun, Jiang, De-li, Chen, Min, Li, Di, Zhang, Jian-xin
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Biomedical and Life Sciences; Biomedicine; Clodronic Acid - administration & dosage; Immunosuppressive Agents - administration & dosage; Liposomes; Lung Injury - diagnosis; Lung Injury - etiology; Lung Injury - prevention & control; Pancreatitis - complications; Pancreatitis - diagnosis; Pancreatitis - drug therapy; Rats; Rats, Sprague-Dawley; Treatment Outcome
• ISSN: 1673-1581; 1862-1783
• DOI: 10.1631/jzus.B1000044

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.