氯化镧拮抗内毒素效应的小鼠体内研究  

Anti-endotoxin effect of lanthanum chloride in vivo: an experimental study of mice

作　　者：汪泱[1] 胡峰[1] 郭菲[2] 袁铿[3] 胡银英[3] 

机构地区：[1]江西医学院第一附属医院泌尿外科研究所,330006 [2]江西医学院第一附属医院烧伤研究所,330006 [3]江西省医学科学研究所

出　　处：《中华医学杂志》2004年第3期242-247,共6页National Medical Journal of China

基　　金：国家自然科学基金资助项目 (3 0 2 60 10 7);江西省自然科学基金资助项目 (0 2 40 0 8)

摘　　要：目的　探讨氯化镧对内毒素 (LPS)体内效应的拮抗作用 ,寻找新的有效内毒素拮抗剂 ,为防治内毒素血症提供实验依据。方法　 (1)观察不同方式给予氯化镧处理对半数致死量LPS(17 5mg/kg)攻击小鼠的死亡率的影响。 (2 )观察氯化镧对LPS(12 5mg/kg)攻击后小鼠血浆肿瘤坏死因α(TNFα)及肝脏TNFαmRNA表达水平的变化、胸腺细胞凋亡状况、肝肺的病理损伤状况的影响。结果　 (1)经 5、10、2 0mg/kg氯化镧处理的半数致死量LPS攻击小鼠的死亡率分别为 0、0和 8% ,明显低于对照组的死亡率 (6 7% ) (P <0 0 1)。 10mg/kg氯化镧预防性给药 ,半数致死量LPS攻击小鼠后死亡率为 2 0 % ,明显低于对照组死亡率 (5 5 % ) (P <0 0 5 )。 (2 )经氯化镧处理的内毒素血症小鼠血浆TNFα含量为 0 4 4± 0 2 15ng/ml,肝组织TNF αmRNA表达量为 (3 9± 0 6 )× 10 5拷贝 / μgRNA ,明显低于内毒素血症小鼠 [0 99± 0 2 4ng/ml,(1 9± 0 3)× 10 7拷贝 / μgRNA],P <0 0 0 1;经氯化镧处理的内毒素血症小鼠胸腺细胞DNA片段百分率为 30 35 %± 6 4 2 % ,明显低于未处理小鼠(5 5 38%± 3 88% ) (P <0 0 0 1) ;内毒素血症小鼠胸腺细胞凋亡百分率为 15 5 6 %± 0 5 9% ,明显高于氯化镧处理小鼠 (6 0 5 %± 0 71% ) (PObjective Lanthanum is one of rare earth with extremely active chemical property and has been evidenced to possess antibacterial effect as well as the function of blocking calcium flux and regulating cellular immunity. Our previous studies showed that lanthanum could affect the biological activity of LPS and inhibit the activity in vitro. In this study, we explored the anti-LPS effects of lanthanum chloride in vivo so as to provide evidence in searching for new anti-endotoxic agents for the prevention and treatment of endotoxemia. Methods (1) 96 BALB/c mice were divided into 2 groups: experimental group including 84 mice injected intraperitoneally with 17.5 mg/kg, LD 50 dose, of LPS mixed with lanthanum chloride of the dosages of 1 mg/kg, 2 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg, 40 mg/kg, and 80 mg/kg respectively; and control group including 12 mice injected intraperitoneally with 17.5 mg/kg of LPS. The mortality rates of different mice within 7 days were observed so as to observe the protective effect of lanthanum chloride (2) 40 BALB/c mice were randomly divided into 2 group2: experimental group injected intraperitoneally with lanthanum chloride of the dosages 10 mg/kg for 3 days and then injected with 1 LD 50 dosage of LPS 30 minutes after the last injection of lanthanum chloride of the dosages 10 mg/kg; and control group injected intraperitoneally with normal saline for 3 days and then with 1 LD 50 dosage of LPS 30 minutes after the last injection of normal saline. The mortality rates of different mice within 7 days were observed. (3) 40 BALB /c mice were randomly divided into 4 groups: LPS group, injected intraperitoneally with LPS of sublethal dosage (12.5 mg/kg), lanthanum chloride treatment group, injected intraperitoneally with LPS of sublethal dosage 1 hour after the venous injection of 10 mg/kg lanthanum chloride, lanthanum chloride control group, injected intravenously with 10 mg/kg lanthanum chloride, and NS control group, injected intraperitoneally with NS. Four hours after the intraperito

关 键 词：氯化镧 内毒素效应 肿瘤坏死因子 单核细胞 内毒素血症 胸腺细胞 感染性休克 

分 类 号：R114[医药卫生—卫生毒理学]