Orionin对急性肝衰竭小鼠的保护作用及其对肝组织细胞因子水平的影响*

目的 探讨冬凌草甲素（Oridonin）对脂多糖/D-氨基半乳糖氨（LPS/D-Gal）联合诱导的急性肝衰竭（ALF）小鼠的保护作用及其对肝组织细胞因子水平的影响。方法 取150只小鼠,随机分成5组,每组 30 只。采用LPS/D-Gal腹腔注射建立小鼠ALF模型,设生理盐水对照组、Oridonin对照组、LPS/D-Gal诱导模型组和LPS/D-Gal处理及不同剂量Oridonin干预组。采用Real-time PCR法检测肝组织肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1α、IL-1β和IL-6 mRNA水平。结果 模型组小鼠48 h存活率为0.0% （0/30）,而两个Oridonin干预组小鼠48 h存活率分别提高至64.5% （19/30）和80.6% （24/30,P<0.01）; 组织病理学检查显示模型组小鼠肝细胞呈大块或/和亚大块坏死,肝小叶结构消失,残存肝细胞肿胀、空泡变性,肝窦肿胀充血,炎细胞浸润。Oridonin干预组小鼠肝细胞坏死、空泡变性和炎细胞浸润等较模型组有明显的改善;模型组小鼠血清ALT和AST水平分别为（345.3 ± 54.1） U/L和（500.2±53.5） U/L,明显高于对照组的（42.3±0.6）U/L和（117.1±9.8）U/L,P<0.01],两个Oridonin干预组分别为 （303.9±39.5） U/L和（340.6±2.8） U/L及（130.2±38.3） U/L和 （209.8±36.2） U/L,P<0.05];模型组小鼠肝组织TNF-α、IL-1α、IL-1β和IL-6 mRNA水平显著高于正常对照组（P<0.01）,而两个Oridonin干预组肝组织TNF-α、IL-1α、IL-1β和IL-6 mRNA水平显著低于模型组 （P<0.01）。结论 Oridonin对LPS/D-Gal诱导的ALF小鼠具有显著的保护作用,其作用机制可能与降低肝组织细胞因子水平有关。

Effect of oridonin on hepatic cytokine levels in mice with LPS/D-Gal-induced acute liver failure

Objective To investigate the effect of oridonin on hepatic cytokine levels in mice with polysaccharide（LPS）/ D-galactosamine（D-Gal）-induced acute liver failure. Methods 150 mice were randomly divided into five groups（30 in each group）,e.g.,normal,oridonin control,model,oridonin-intervened,and oridonin-intervened for 12 days. ALF model was established in C57BL/6 mice by intraperitoneal injection of LPS/D-Gal. Results The 48 h lethality rate in LPS/D-Gal-induced group reached an extremely high level of 100%. However,the 48 h survival rates in two oridonin-intervened groups were 64.5% （19/30） and 80.6% （24/30,P<0.01）;The damage in liver tissues was ameliorated in mice pretreated with oridonin as compared with that in the model group;Serum ALT and AST levels in model group were（345.3±54.1） U/L and（500.2±53.5） u/L,significantly higher than those in control group（42.3±0.6） U/L and（117.1±9.8） U/L,P<0.01] or in oridonin-treated group （303.9±39.5） U/L and （340.6±2.8） U/L or （130.2±38.3） U/L and （209.8±36.2） U/L,P<0.05];Administration of oridonin in mice with LPS/D-Gal-induced ALF significantly decreased mRNA levels of hepatic TNF-α,IL-1α, IL-1β and IL-6 compared with in model group（P<0.01）. Conclusion Oridonin has a protective effect on mice with LPS/D-Gal-induced ALF,and the mechanism might be related to inhibition of hepatic cytokine activities.