丹皮酚对大鼠肝纤维化治疗作用的实验研究

覃星柳杨萍1

(广西壮族自治区贵港市人民医院药剂科，广西贵港537100)

【摘要】目的探讨丹皮酚对大鼠肝纤维化的治疗作用及其机制。方法将33只大鼠随机分为正常组、模型对照组、丹皮酚干预组，每组11只，模型对照组及丹皮酚干预组采用四氯化碳(CCl4)诱导建立肝纤维化模型。建模结束后，丹皮酚干预组予4 000 mg/kg丹皮酚灌胃，正常组及模型对照组予相同容积0.9%氯化钠注射液灌胃。连续灌胃2周后，观察比较3组大鼠体质量、肝质量及肝指数，测定血清肝纤维化生化指标血清Ⅲ型前胶原肽(PⅢP)、层黏连蛋白(LN)、Ⅳ型胶原蛋白(collagens Ⅳ)及透明质酸(HA)水平，肝组织氧化应激指标超氧化物歧化酶(SOD)、谷胱甘肽转移酶(GST)、谷胱甘肽(GSH)及丙二醛含量(MDA)，肝组织病理切片行马松(Masson)三色染色检测肝纤维化情况，逆转录酶-聚合酶链反应(RT-PCR)检测collagens Ⅰ mRNA的表达。结果造模后，模型对照组及丹皮酚干预组大鼠体质量均低于正常组，肝质量及肝指数均高于正常组(P<0.05)，但丹皮酚干预组肝指数增加幅度低于模型对照组(P<0.05)；模型对照组及丹皮酚干预组肝组织Masson染色胶原纤维较正常组均明显增加(P<0.05)，但丹皮酚干预组增加情况低于模型对照组(P<0.05)；模型对照组及丹皮酚干预组大鼠血清肝纤维化生化指标PⅢP、LN、collagens Ⅳ及HA水平较正常组均明显增高(P<0.05)，但丹皮酚干预组增加幅度均低于模型对照组(P<0.05)；模型对照组及丹皮酚干预组collagens Ⅰ mRNA表达较正常组均显著升高(P<0.05)，但丹皮酚干预组collagens Ⅰ mRNA表达增加幅度低于模型对照组(P<0.05)；模型对照组及丹皮酚干预组大鼠肝组织MDA、GST水平较正常组均显著升高(P<0.05)，GSH、SOD水平均显著降低(P<0.05)，但丹皮酚干预组MDA、GST升高幅度及GSH、SOD降低幅度均低于模型对照组(P<0.05)。结论丹皮酚可以缓解CCl4诱导的大鼠肝纤维化过程，其作用机制可通过降低氧化应激水平，增强抗氧化作用来改善肝纤维化进程。

【关键词】牡丹皮；肝硬化；大鼠；疾病模型，动物

doi：10.3969/j.issn.1002-2619.2015.04.025

【中图分类号】R285.5

【文献标识码】A

【文章编号】1002-2619(2015)04-0546-04

作者简介：覃星柳(1972—)，女，副主任药师，学士。从事药剂科工作。

Abstract【】Objective To study the therapeutic effects and mechanism of paeonol on hepatic fibrosis rats.Methods 33 rats were randomly divided into normal group, model group and paeonol intervention group, 11 rats in each group.Liver Fibrosis model in model group and paeonol intervention group were induced by carbon tetrachloride (CCl4).After modeling, rats in paeonol intervention group received paeonol (4 000 mg/kg) via gastrogavage, rats in other two groups received 0.9% sodium chloride injection via gastrogavage at the same dose.After 8 weeks of gastric perfusion, the level of body mass, liver mass and liver index in rats were observed in three groups.The level of the serum liver fibrosis biochemical index like serum procollagen type Ⅲ peptide (PⅢP), laminin lens (LN), collagens Ⅳ and hyaluronic acid (HA),and the degree of the liver tissue oxidative stress index like superoxide dismutase (SOD), glutathione-transferase (GST), glutathione (GSH) and malondialdehyde content (MDA) were detected in three groups, the liver fibrosis degree of liver tissue pathological section was detected by masson's trichrome staining, and the expression of collagensⅠmRNA was detected by inverse transcriptase-polymerase chain reaction (RT-PCR).Results After modeling, the level of rats body mass in model group and paeonol intervention group was lower than that in normal group (P<0.05), the level of liver mass and liver index were increased (P<0.05), but the increase of liver index in paeonol intervention group was lower than that in model group (P<0.05).Masson's staining collagen fiber of liver tissue in model group and paeonol intervention group was significantly increased as compared with that in normal group (P<0.05), but the increase in paeonol intervention group was lower than that in model group (P<0.05).The degree of PⅢP, LN, collagens Ⅳ and HA in model group and paeonol intervention group were significantly increased as compared with those in normal group (P<0.05), but the increase in paeonol intervention group was lower than that in model group (P<0.05).The expression of collagensⅠmRNA in model group and paeonol intervention group was significantly increased as compared with that in normal group(P<0.05), the increase in paeonol intervention group was lower than that in model group (P<0.05).The level of MDA, GST of rats liver tissue in model group and paeonol intervention group were significantly increased as compared with those in normal group (P<0.05), the level of GSH, SOD were decreased (P<0.05), but the change range in paeonol intervention group was smaller than that in model group (P<0.05).Conclusion Paeonol can relief carbon tetrachloride-induced liver fibrosis degree in rats through the action mechanism of decreasing oxidative stress level and enhance antioxidation effect.

收稿日期：(2013-12-26)

1广西壮族自治区贵港市中西医结合骨科医院药剂科，广西贵

港537100

Experimental study of the therapeutic effects of paeonol on hepatic fibrosis ratsQINXingliu*,YANGPing.*DepartmentofPharmacy,People'sHospitalofGuigangCity,Guangxi,Guigang537100

【Key words】 Cortex moutan；Liver cirrhosis；Rat；Disease model；Animal

丹皮酚是中药毛莨科植物牡丹的根皮和萝摩科植物徐长卿干燥根及根茎中的主要有效成分，是一种小分子酚类化合物，化学名称为2-羟基-4-甲氧基苯乙酮，分子量166，分子式C9H10O3。现代医学表明，丹皮酚具有镇静催眠、解热镇痛、抗菌消炎、免疫调节、抗氧化及保护心脑血管等药理活性[1-3]，对多种慢性肝病和病毒性肝炎也具有良好的治疗和预防作用[4-6]。……