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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 protective effect of Oridonin on acute liver failure (ALF) induced by lipopolysaccharide / D-galactosamine (LPS / D-Gal) in mice and its effect on the level of cytokines influences. Methods 150 mice were randomly divided into 5 groups of 30 rats. The model of ALF was established by intraperitoneal injection of LPS / D-Gal. The normal saline control group, Oridonin control group, LPS / D-Gal induced model group and LPS / D-Gal treatment group and different doses of Oridonin intervention group were established. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL) -1α, IL-1β and IL-6mRNA in liver tissue were detected by Real-time PCR. Results The survival rate of mice in model group at 48 h was 0.0% (0/30), while the survival rate of mice in two Oridonin groups increased to 64.5% (19/30) and 80.6% (24/30, P < 0.01). Histopathological examination showed that the hepatocytes in the model group were necrotic in chunks and / or subunits, the hepatic lobules disappeared, the remaining hepatocytes were swollen, vacuolar degeneration, hepatic sinusoid hyperemia and inflammatory cell infiltration. The levels of ALT and AST in serum of model group were (345.3 ± 54.1) U / L and (500.2 ± 53.5) U / L respectively, compared with those of Oridonin intervention group U / L was significantly higher than that in the control group [(42.3 ± 0.6) U / L and (117.1 ± 9.8) U / L, P <0.01] (340.6 ± 2.8) U / L and [(130.2 ± 38.3) U / L and (209.8 ± 36.2) U / L respectively, P <0.05]. The levels of TNF-α, IL-1α and IL- (P <0.01). The levels of TNF-α, IL-1α, IL-1β and IL-6mRNA in the two Oridonin intervention groups were significantly lower than those in the untreated group (P <0.01). Conclusion Oridonin has a significant protective effect on LPS / D-Gal-induced ALF mice, and its mechanism may be related to reducing the level of cytokines in liver tissue.