金属硫蛋白在细菌脂多糖引发肝脏损伤中的作用

Protective effects of metallothionein against lipopolysaccharide-induced acute liver injury

目的探讨金属硫蛋白(Metallothionein,MT)对细菌脂多糖(Lipopolysaccharide,LPS)引起的肝脏损伤的影响及其可能机制。方法利用MT基因敲除(MT-/-)小鼠及与之对应的野生型(MT+/+)小鼠腹腔注射LPS(10 mg/kg)造成急性肝损伤模型,通过测定不同时间点血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活力,肝脏丙二醛(MDA)含量,以及肝脏组织病理学检查结果,判断LPS对两种小鼠肝脏损伤程度的差异。结果LPS可以使两种小鼠血清酶ALT、AST活力均呈时间依赖性升高,肝脏内脂质过氧化产物增加。组织病理学检查显示,肝脏出现肝细胞浊肿,空泡变性,液化坏死,星状细胞增生。MT+/+小鼠血清ALT,AST升高趋势较MT-/-小鼠更为显著。炎症反应早期MT-/-小鼠肝组织内炎性细胞浸润程度轻于MT+/+小鼠,随炎症反应时间延长,MT-/-小鼠较MT+/+小鼠肝组织损伤程度呈加重趋势。LPS致MT-/-小鼠肝脏脂质过氧化程度较MT+/+小鼠更为严重。结论MT对LPS引起的肝脏损伤具有一定的保护作用,其可能机制与MT增强机体清除LPS能力以及对LPS致炎过程中生成的ROS的清除作用有关。

Objective To investigate the role of metallothionein （MT） in lipopolysaccharide （LPS）-in.duced acute liver injury. Method 6 ～ 8 weeks MT gene knocked out mice （ MT - / - ） and the corresponding wild-type mice （ MT ＋ / ＋ ） were treated with LPS 10 mg/kg（i.p. ） or equal volume of saline respectively. Animal serum was collected for alanine aminotransferase（ALT） and aspartate aminotransferase（AST） analyses. Liver tissues were removed for malondialdehyde （MDA） measurement and histopathological examination. Results After the challenge of LPS, serum ALT, AST were significantly lower in MT - / - mice than in MT ＋ / ＋ . The content of MDA in liver was significantly higher in MT - / - mice than in MT ＋ / ＋ . MT - / - mice showed more significant necrosis and degeneration than MT-wt after 24 h challenge of LPS, however MT-wt mice presented more inflammatory cell recruitment 6 h after the challenge of LPS. Conclusion MT can alleviate LPS-induced hver injury, and possibly through the ability of scavenging reactive oxygen species.