氯化钆保护细菌脂多糖引发肝脏损伤及其可能机制研究  

Gadolinium chloride pretreatment prevents lipopolysaccharide(LPS)-induced acute liver injury in both metallothionein(MT)-null and wild-type mice

作　　者：郭隽[1,2,3] 帅怡[2] 张立实[2] 彭双清[1] 

机构地区：[1]军事医学科学院疾病预防与控制所,北京100071 [2]四川大学华西公共卫生学院 [3]中国食品药品检定研究院国家药物安全评价监测中心

出　　处：《毒理学杂志》2014年第6期438-442,共5页Journal of Toxicology

基　　金：国家自然科学基金(30572281)

摘　　要：目的探讨氯化钆(Gadolinium chloride,Gd Cl3)在细菌脂多糖(Lipopolysaccharide,LPS)引起肝脏损伤的影响及其机制。方法将MT基因敲除小鼠(MT-/-)及与之对应的野生型小鼠(MT+/+)各分为4组:生理盐水对照组、LPS染毒组、Gd Cl3组和Gd Cl3预处理+LPS染毒组。动物腹腔注射LPS(10 mg/kg,腹腔注射)或生理盐水(NS,腹腔注射),此前24 h给予Gd Cl3(10 mg/kg,尾静肪注射)或NS预处理。注射LPS后24 h测定血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活力以及一氧化氮(NO)含量,镉饱和法测定肝脏金属硫蛋白(MT)含量,进行肝组织病理学检查,判定不同处理对MT-/-小鼠及MT+/+小鼠肝脏影响的差异。结果注射LPS后,MT-/-小鼠及MT+/+小鼠血ALT、AST活力,血NO含量均较对照组升高,两种小鼠肝组织均出现大量炎性细胞浸润、肝细胞浊肿、空泡变性、灶性液化坏死、星状细胞增生。组织病理学检查结果显示MT-/-小鼠肝组织损伤程度较MT+/+小鼠更为严重。氯化钆、LPS均可以诱导MT+/+小鼠肝脏MT生成。Gd Cl3预处理可以同时降低LPS对MT-/-小鼠及MT+/+小鼠血ALT,AST活力,血NO含量的影响,可以减轻LPS对两种小鼠肝组织病理学损伤。结论 Gd Cl3预处理可以有效减轻由LPS引起的肝脏损伤,MT通过其对Kuffer细胞的抑制作用保护LPS引起的肝脏损伤。Objective To investigate the role of gadolinium chloride （GdC13 ） in lipopolysaccharide （LPS）-induced acute liver injury. Methods 6 - 8 week MT gene knocked out mice （ MT - / - ） and corresponding wild-type mice （ MT ＋ / ＋ ） divided into 4 groups respectively and were pretreated with either saline or GdCI3 （10 mg/kg iv） at 24 h before the administration of LPS （10 mg/kg, i. p. ） or equal volume of saline. 24 h after the challenge of LPS and serum and livers were collected for analysis. The levels of serum ALT, AST, .NO and liver MT were measured. The liver was fixed for microscopic examination. Results Serum ALT,AST,NO significantly increased after the challenge of LPS in both MT - / - mice and MT ＋ / ＋ mice. MT - / - mice showed more significant necrosis and degeneration than MT ＋ / ＋ mice after 24 h challenge of LPS. GdC13 and LPS can induce MT synthesis in MT ＋ / ＋ mice. Pretreatment of GdC13 can decrease serum ALT, AST, NO levels in both MT-null mice and MT-wt after the challenge of LPS. Histopathologieal examination showed that GdC13 pretreatment can alleviate LPS-induced liver damage in both type. Conclusion GdC13 act as a protective role in LPS-induced liver injury in both MT-null and MT-wt mice, and possibly through the inhibition of kuffer cell.

关 键 词：氯化钆 金属硫蛋白 细菌脂多糖 肝 

分 类 号：R114[医药卫生—卫生毒理学]