NF-κB在MT对LPS致肝脏炎症损伤保护效应中的作用

The role of NF-κB in protective effect of MT in LPS-induced rat liver injury

目的采用NF-κB特异性抑制剂PDTC,观察NF-κB在MT保护LPS急性肝脏损伤中保护效应的作用机理。方法 MT+/+小鼠和MT-/-小鼠各分为4组,在注射LPS前30 min,腹腔注射PDTC 40 mg/kg,LPS剂量为10 mg/kg,24 h后处死动物。结果 PDTC预处理可以降低两种小鼠血清酶ALT、AST活性,减少血液中TNF-α、IL-1β、IL-6等细胞因子,血清以及肝脏组织中NO含量,降低肝组织TNF-α表达量,同时减轻两种小鼠肝脏组织病理学损伤程度,减轻肝组织内脂质过氧化产物生成量。以PDTC预处理消除MT自由基清除作用对NF-κB转录活性的影响后,不能观察到两种小鼠NF-κB转录活性间的差异,其未见两种小鼠肝脏损伤程度的差异。结论 MT可能通过其自由基清除作用调控NF-κB信号通路,从而影响整个炎症反应网络,造成了LPS致两种小鼠肝脏炎症损伤程度间的差异。

Objective To observed the role of NF-κB signaling pathway in MT protection LPS protective effect of acute liver injury.Methods 6-8 weeks MT gene knocked out mice（ MT- /-） and corresponding wild-type mice（ MT ＋ / ＋） were divided into 4 groups respectively and were pretreated with either saline or PDTC（ 40 mg /kg i. p.） at 30 min 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. Results The levels of serum enzyme,cytokines,NO and liver cytokines,NO,and MDA were measured. The liver was fixed for microscopic examination. Pretreatment of PDTC can decrease serum enzyme,cytokines,NO levels in both MT-null mice and MT-wt after the challenge of LPS. Histopathological examination showed that PDTC pretreatment can inhibit LPS-induced NF-κB activation and alleviate LPS-induced liver damage in both type.Conclusion MT may exert the protective effect of LPS-induced acute liver injury through the NF-κB pathway.