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

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

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 m RNA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 m RNA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 m RNA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。

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.