联合应用粉防己碱与甘草酸抗肝纤维化分子生物学机制研究

Biological Mechanisms of Combination of Tetrandrine and Glycyrrhizinic Acid against Hepatic Fibrogenesis Induced by Carbon Tetrachloride in Rats

目的 探讨联合应用粉防己碱 (tetrandrine,Tet)与甘草酸 (glycyrrhizinicacid ,Glz)抗肝纤维化的分子生物学机制。方法 采用四氯化碳皮下注射诱导大鼠肝纤维化模型 ,同时给予不同剂量 (5mg/kg、10mg/kg、2 0mg/kg体重 )Tet、(5 0mg/kg体重 )Glz及二者联合灌胃或腹腔注射 ,用RT PCR法检测肝组织Ⅰ型、Ⅲ型前胶原、c fos及c junmRNA表达。结果 (10mg/kg、2 0mg/kg体重 )Tet和Glz单独应用能够不同程度抑制肝纤维化大鼠肝组织Ⅰ型、Ⅲ型前胶原、c fos及c junmRNA表达 ,两种药物联合应用效果更为显著。结论 联合应用Tet与Glz能够更有效地在转录及其上游水平抑制肝脏胶原合成。

Objective To investigate biological mechanisms of combination of tetrandrine and glycyrrhizinicacid against hepatic fibrogenesis in rats.Methods The fibrotic model was induced with carbon tetrachloride in rats, and different doses of 5 mg/kg, 10 mg/kg, or 20 mg/kg body weight Tet, 50 mg/kg body weight Gly were given alone or simultaneously by daily gavage or/and peritoneal injection. MRNA expressions of collagen type I, Ⅲ c fos and c jun were evaluated by RT PCR.Results mRNA levels of type I procollagen, type Ⅲ procollagen, c fos, and c jun were significantly higher in rats of the model group, as compared with those of control group. In contrast, the increase of mRNA level in drug treated rats was significantly less than those in rats of the model group.Conclusion A combination of Tet and Gly can more effectively down regulated type I and type Ⅲ collagen synthesis at transcription and its upstream levels.