绿原酸对大鼠阻塞性黄疸导致的肝纤维化的治疗作用  

Effects of chlorogenic acid on hepatic fibrosis in the rats with obstructive jaundice

作　　者：吴多虎[1] 鲍传裕[1] 李龙鹤[1] 邹永平[1] 袁巍[1] 王德森[1] 谢晋元 宫晓光[1] 

机构地区：[1]海南省人民医院急诊科,海口570311

出　　处：《山西医科大学学报》2016年第11期963-967,共5页Journal of Shanxi Medical University

基　　金：2014年海南省应用技术研发与示范推广专项(ZDXM2014066)

摘　　要：目的探索绿原酸(CA)对阻塞性黄疸导致的肝纤维化模型大鼠治疗作用及其作用机制。方法 Wistar大鼠行胆总管结扎手术复制阻塞性黄疸肝纤维化模型,随机分为模型组、水飞蓟宾组(Sil,50 mg/kg)、绿原酸低、中和高剂量组(37.5,75,150 mg/kg),同时设假手术对照组。除模型组和对照组外,其他各组大鼠均按10 ml/kg体重灌胃相应剂量药物,持续4周。实验结束后计算肝脏指数,HE观察肝脏损伤及Masson观察纤维化程度,RT-PCR技术检测肝脏Ⅰ和Ⅲ型胶原、VEGF、TGF-β1的mRNA水平,免疫印迹法检测α-SMA蛋白的表达水平。结果胆总管结扎术诱导模型大鼠肝脏指数明显增加,肝组织出现明显病理改变,并伴有纤维化发生;与模型组相比,绿原酸中高剂量组肝脏指数明显降低,肝小叶结构清晰,炎症细胞浸润减少,肝小叶结构破坏缓解,同时Ⅰ、Collagen Ⅲ、TGF-β1、VEGF mRNA水平,α-SMA蛋白的表达显著降低(P<0.05)。结论绿原酸在可通过抑制TGF-β1、VEGF和α-SMA的表达从而降低胆总管结扎诱导的肝纤维化病变的风险。Objective To explore the protective effects of chlorogenic acid（ CA） on hepatic fibrosis in rats with obstructive jaundice.Methods A total of 66 rats were randomly divided into sham group,model group,silibinin group,low,moderate and high CA groups. The hepatic fibrosis models were established by bile duct ligation（ BDL）. The rats in silibinin group were treated with 50 mg /kg silibinin and the rats in CA groups were treated with 37. 5,75 mg / kg and 150 mg / kg CA for 4 weeks,respectively. In order to assess the effect of CA on liver damage and fibrosis,the liver index,HE and Masson staining were observed. Moreover,the mRNA levels of collagen Ⅰ,Ⅲ,VEGF and TGF-β1 were detected by RT-PCR,and the level of α-SMA was detected by Western blot. Results The liver index in model group increased highly compared to sham group（ P〈0. 001）,and there was obvious pathological changes in liver tissues and hepatic fibrosis. The liver index in moderate and high dose groups significantly deceased compared to model group（ P〈0. 01）,and the inflammatory cell infiltration and the damage of lobuli hepatic was reduced. The expression of collagen Ⅰ,collagen Ⅲ,VEGF and TGF-β1 mRNA,and α-SMA protein were decreased in high dose group（ P〈0. 01）. Conclusion The results suggest that CA may exhibit a therapeutic potential for liver fibrosis by inhibiting the production of TGF-β1,VEGF and α-SMA.

关 键 词：绿原酸 阻塞性黄疸 肝纤维化 

分 类 号：R575[医药卫生—消化系统]