Clodronate—SPIO脂质体对重症急性胰腺炎大鼠肝损伤的保护作用及MRI评价

Protection of SPIO-clodronate liposome against liver injury in rats with severe acute pancreatitis and its evaluation by MRI

摘要：目的 探讨Clodronate-SPIO脂质体对重症急性胰腺炎（SAP）大鼠肝损伤的保护作用及磁共振成像（MRI）对肝损害程度的评价.方法 利用化学共沉淀法制备超顺磁性Fe3O4纳米微粒.利用薄膜法制备Clodronate-SPIO脂质体.采用胰腺被膜下均匀注射（2 ml/kg体重）牛磺胆酸钠制作SAP模型.将SD大鼠随机分为对照组、SAP-SPIO脂质体组、SAP＋Clodronate-SPIO脂质体组.6 h后对各组大鼠肝脏的相同层面进行MRI扫描,测定T2WI.扫描结束后,取肠系膜上静脉血液检测各组大鼠血清中ALT、AST的含量,观察肝脏和胰腺组织的病理学变化.结果 透射电镜检查见脂质体大小均匀.对照组胰腺未见明显改变,SAP＋Clodronate-SPIO脂质体组大鼠的胰腺及肝脏病理变化均较SAP-SPIO脂质体组明显减轻.SAP＋SPIO脂质体组6 h ALT和AST含量较对照组明显升高（P＜0.01）;SAP＋Clodronate-SPIO脂质体组血清ALT和AST水平均显著低于SAP＋SPIO脂质体组（P＜0.01）.肝组织信号强度SAP＋SPIO脂质体组及SAP＋Clodronate-SPIO脂质体组较对照组明显减低,SAP＋Clodronate-SPIO脂质体组信号强度较SAP＋SPIO脂质体组降低（P＜0.01）.结论 Clodronate脂质体对SAP大鼠肝损害有保护作用,SPIO可作为MRI检查的示踪剂.

Objective To investigate the protective effect of clodronate SPIO liposomes on liver injury of rats with severe acute pancreatitis（SAP）and the role of MRI in evaluating the extent of liver injury.Methods Superparamagnetic Fe3O4 nanoparticles were prepared by chemical coprecipitation.Clodronate-SPIO-containing liposomes was prepared by the thin-film method.SAP models were prepared by a uniform injection of sodium taurocholate（2 ml/kg body weight）into the subcapsular space of the pancreas.SD rats were randomly divided into control group,SAP plus SPIO group, and clodronate-SPIO-containing liposome group.Six hours after SAP models were available,T2-weighted MRI scanning（in the same plane）of the liver of rats in each group were performed.At the end of the scanning,blood samples were taken from the supcrior mesenteric vein to measure the contents of serum ALT and AST.Meanwhile, The pathological changes in the liver and pancreas were observed.Results Transmission electron microscopic examination showed that liposomes had a uniform size.No changes in the pancreas of rats in control group were noted.The pathological changes in the pancreas and liver of rats in SAP plus clodronate-SPIO-containing liposome group were significantly milder than those in SAP plus SPIO liposome group.The contents of serum ALT and AST in rats in SAP plus SPIO liposome group were significantly higher than those in control group（P〈0.01）, while the contents of serum ALT and AST in rats in SAP plus clodronate-SPIO-containing group were significantly lower than those in SAP plus SPIO liposome group（P〈0.01）.The MRI signal intensity of the liver in SAP plus SPIO liposome group and SAP plus clodronate-SPIO-containing liposome group was significantly lower than that in control group.The significant changes in the MRI signal intensity of the liver in SAP plus SPIO liposome group and SAP plus Clodronate-SPIO liposome group were noted（P〈0.01）.Conclusion Clodronate-containing liposomes have protective effects against liver injury in SAP rats and SPIO can be used as a tracer for MRI examination.