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

作　　者：Sheng-chun DANG De-li JIANG Min CHEN Di LI Jian-xin ZHANG 

机构地区：[1]Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China [2]School of Chemistry and Chemical Engineering, Jiangsu University, Zhenj iang 212013, China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2010年第11期828-835,共8页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：Project supported by the National Natural Science Foundation of China(No.30772117);the Science Foundation of Jiangsu Province of China(No.BK2007096)

摘　　要：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 strObjectives: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 Pgroup,and clodronate-containing liposome to the Tgroup 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-αwere significantly increased in the Pgroup compared to those in the Tgroup(P<0.05) .In the Tgroup,large numbers of TUNEL-positive cells were observed,but no or few in the C and Pgroups.Gross inspection and H&E staining of pancreata and lung showed dramatic tissue damage,including inflammation and necrosis in the Pgroup.Less remarkable changes were noted in the Tgroup,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 Tgroup.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.

关 键 词：PANCREATITIS Clodronate disodium MACROPHAGE Lung injury 

分 类 号：R56[医药卫生—呼吸系统]