摘要目的 研究大麻素受体-2 (CB2)激动剂AM1241对四氯化碳(CCl4)诱导的实验性肝纤维化小鼠肝组织中血小板衍生生长因子(PDGF)、Ⅲ-型胶原(Col-Ⅲ)基因与蛋白表达的影响. 方法 38只8周龄C57BL/6J雄性小鼠随机分为对照组、模型组、CB2受体激动剂(AM1241)3 mg/kg组、9 mg/kg组.除对照组外,其余组用30％CCh复制肝纤维化模型,每周3次,5ml/kg,共16周,造模同时CB2受体激动剂干预组每天分别给予3mg/kg、9 mg/kg AM1421,按实际体质量调整给药腹腔注射,对照组采用相同溶剂和方法.采用血清酶学检测血清天冬氨酸氨基转移酶(AST),采用组织切片苏木素-伊红染色观察小鼠肝脏炎症情况及纤维化程度,利用Real-time PCR和免疫组织化学法检测PDGF、Col-Ⅲ基因和蛋白在肝组织中的表达水平.多组间比较采用单因素方差分析.结果 与对照组相比,模型组肝纤维化程度严重、血清AST均明显增高[(742±300.8) U/L对比(118.1±31.1) U/L] (P＜0.05),肝组织PDGF、Col-ⅢmRNA和蛋白的表达均明显增强(P＜0.05);与模型组比较,AM1241 3mg/kg组、9mg/kg组肝纤维化程度明显减轻,血清AST明显降低[分别为(116.6±13.68) U/L对比(742±300.8) U/L,(113.8±16.01) U/L对比(742±300.8) U/L](P＜ 0.05),肝组织PDGF、Col-ⅢmRNA和蛋白的表达均有所降低(P＜0.05). 结论 CB2受体激动剂AM1241可抑制肝纤维化小鼠肝组织PDGF基因和蛋白的表达,使细胞外基质合成减少.

abstractsObjective To investigate the effect of cannabinoid receptor-2 (CB2) agonist AM1241 on the mRNA and protein expression of platelet-derived growth factor (PDGF) and collagen-H (Col-Ⅲ) in the liver tissue of mice with experimental liver fibrosis induced by carbon tetrachloride (CCL).Methods Totally 38 8-week-old male C57BL/6J mice were randomly divided into control group,model group,3 mg/kg CB2 receptor agonist (AM1241) group,and 9 mg/kg AM1241 group.All mice,except for the control group,were treated with 30％ CC14 (three times a week,5 ml/kg body weight,16 weeks) to establish a liver fibrosis model.Meanwhile,3 and 9 mg/kg AM 1421 was intmperitoneally injected for daily intervention,respectively.The dosage was adjusted according to actual body weight.The same solvent was given in the control group.The serum level of aspartate aminotransferase (AST) was measured by serum enzyme digestion.The liver inflammation and fibrosis were observed by HE staining of tissue slices.The mRNA and protein expression of PDGF and Col-Ⅲ in hepatic tissue was determined by real-time PCR and immunohistochemistry.Results Compared with the control group,the mice in model group showed severe liver fibrosis,significantly elevated serum AST level (742 ± 300.8 U/L vs 118.1 ± 31.1 U/L,P ＜ 0.05),and significantly increased mRNA and protein expression of PDGF and ColⅢ in liver tissue (P ＜ 0.05).Compared with the model group,the mice in 3 mg/kg AM1241 group and 9 mg/kg AM 1241 group had less severe liver fibrosis,and significantly reduced serum AST levels (116.6 ± 13.68 U/L vs 742 ± 300.8 U/L,P ＜ 0.05;113.8 ± 16.01 U/L vs 742 ± 300.8 U/L,P ＜ 0.05) and mRNA and protein expression of PDGF and Col-Ⅲ in liver tissue (P ＜ 0.05).Conclusion CB2 receptor agonist AM1241 can inhibit the mRNA and protein expression of PDGF in the liver tissue of mice with hepatic fibrosis,and reduce extracellular matrix synthesis.