载氯膦酸盐脂质体减轻重症急性胰腺炎大鼠的肺损伤。
Clodronate-containing liposomes attenuate lung injury in rats with severe acute pancreatitis.
机构信息
Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang, China.
出版信息
J Zhejiang Univ Sci B. 2010 Nov;11(11):828-35. doi: 10.1631/jzus.B1000044.
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.
目的
重症急性胰腺炎（SAP）可导致急性肺损伤（ALI）。本文旨在研究载氯膦酸脂质体对 SAP 大鼠 ALI 的保护作用。
方法
采用薄膜法制备脂质体。将 Sprague-Dawley 大鼠随机分为 3 组，通过向胰腺被膜下腔注射 5%（w/v）牛磺胆酸钠（2 ml/kg 体重）建立 SAP 模型后，对照组（C 组）给予生理盐水，磷酸盐缓冲液（PBS）脂质体组（P 组）给予 PBS 脂质体，载氯膦酸脂质体组（T 组）给予载氯膦酸脂质体经尾静脉给药。分别于 2、6 h 从肠系膜上静脉取血，检测血清淀粉酶、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平。苏木精-伊红（H&E）染色观察胰腺和肺组织的形态学变化，末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法（TUNEL）检测细胞凋亡。此外，用免疫组织化学法检测肺组织中巨噬细胞标志物 CD68。
结果
与 T 组相比，P 组血清淀粉酶、IL-6、TNF-α水平明显升高（P<0.05）。T 组可见大量 TUNEL 阳性细胞，而 C 组和 P 组未见或仅见少数 TUNEL 阳性细胞。胰腺和肺的大体观察和 H&E 染色显示 P 组有明显的组织损伤，包括炎症和坏死，而 T 组损伤较轻，C 组组织学正常。Kaiser 标准的组织学评分与 H&E 结果一致。T 组 CD68 阳性巨噬细胞数量减少。
结论
载氯膦酸脂质体对 SAP 大鼠 ALI 具有保护作用。阻断巨噬细胞可能是 SAP 的一种新的治疗策略。
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