氯膦酸二钠脂质体对重症急性胰腺炎大鼠脑损伤的保护作用

Protective effects of clodronate-liposome on cerebral damage induced by severe acute pancreatitis in rats

目的:探讨氯膦酸二钠脂质体对重症急性胰腺炎(severe acute pancreatitis,SAP)大鼠脑损伤的保护作用。方法:利用薄膜法制备氯膦酸二钠脂质体。将48只健康雄性SD大鼠随机分为3组:假手术组、空白脂质体组(LB组)和氯膦酸二钠脂质体组(LC组)。LB组和LC组采用胰腺被膜下均匀注射5%牛磺胆酸钠(2 m L/kg)制备SAP模型,假手术组仅模拟注射操作。LB组在建模后立即于大鼠尾静脉内注射空白脂质体(4 m L/kg),LC组注射氯膦酸二钠脂质体(4 m L/kg)。制模后2 h、6 h取肠系膜上静脉血液,检测各组大鼠血清中淀粉酶、IL-6、肿瘤坏死因子-α(TNF-α)的含量;观察各组胰腺组织的病理学变化及胰腺病理学评分;检测脑组织的含水量、伊文氏蓝浓度和脑脊液中髓鞘碱性蛋白(myelin basic protein,MBP)含量。结果:LB组较假手术组2 h、6 h血清淀粉酶、IL-6、TNF-α含量及胰腺病理学评分均显著增高(P<0.01),LC组较LB组2 h、6 h血清淀粉酶、IL-6、TNF-α含量及胰腺病理学评分均显著降低(P<0.01);LB组较假手术组2 h、6 h脑组织的含水量、伊文氏蓝浓度及脑脊液MBP含量均显著增高(P<0.01),LC组较LB组2 h、6 h脑组织的含水量、伊文氏蓝浓度及脑脊液MBP含量均显著降低(P<0.01)。结论:氯膦酸二钠脂质体可选择性清除单核-巨噬细胞,对SAP大鼠脑组织损伤有保护作用。

Objective： To investigate the protective effects of clodronate-liposome on cerebral damage in- duced by severe acute pancreatitis（SAP） in rats. Methods： Clodronate-liposome was prepared by means of thin film. The models of SAP were performed by prinking injection of 5% sodium taurocholate （2 mL/kg） into the pancreatic capsule. A total of 48 male healthy SD rats were randomly divided into the sham group （Sham） , SAP ＋ liposome group （ LB）, SAP ＋ clodronate-liposome group （LC）. LB group were injected with liposome （4 mL/kg） while LC group were injected with clodronate-liposomes （4 mL/kg） in tail vein immediately after the SAP model performed. The change of amylase （AMS） in serum and the level of IL-6, TNF-a were obtained at 2 h and 6 h after operation, respectively. Pathologic alteration of pancreas was ob- served and pathological score of pancreatic tissue was also estimated. The water and Evan＇s blue content of brain tissues, the content of myelin basic protein （MBP） in cerebrospinal fluid were detected. Results： Compared with Sham group, the serum levels of AMS, IL-6, TNF-α and pancreatic tissue pathological score were significant elevated at 2 and 6 hours in LB group（P 〈0.01 ）. In LC group, the serum levels of AMS, IL-6, TNF-α and pancreatic tissue pathological score were significant decreased at 2 and 6 hours compared with LB group（P 〈 0.01 ）. Compared with Sham group, the water and Evan＇s blue content of brain tissues, the content of MBP in cerebrospinal fluid were significant elevated at 2 and 6 hours in LB group （P 〈0.01 ）. In LC group, the water and Evan＇s blue content of brain tissues, the content of MBP in eerebrospi- nal fluid were significant decreased at 2 and 6 hours compared with LB group （ P 〈 0.01 ）. Conclusion： Monocytes/macrophages can be depleted by phagocytosis of liposome encapsulated clodronate, which may contribute to protection of clodronate-liposome against cerebral damage caused by SAP in rats.