羟基红花黄色素A对四氯化碳致大鼠肝纤维化的干预作用

Effect of hydroxysafflor yellow A intervention in rats with hepatic fibrosis induced by CCl4

目的：探讨羟基红花黄色素A（HYSA）对四氯化碳（CCl4）诱导的大鼠肝纤维化（HF）形成的影响及其机制。方法：清洁级雄性SD大鼠随机分为模型组、红花注射液组、HYSA组和秋水仙碱组，腹腔注射给药，8周后取材，放射免疫技术检测血清纤维化指标透明质酸（HA）、层黏蛋白（LN）、Ⅲ型前胶原（PC-UI）、Ⅳ型胶原（CIV），Masson三色染色观察胶原纤维面积比变化，Hoechest33342染色荧光显微镜观察肝细胞凋亡情况，免疫组织化学法检测肝组织基质金属蛋白酶组织抑制因子（TIMP-1）的表达情况。结果：与生理盐水组比较，红花注射液组、HYSA组和秋水仙碱组大鼠血清HA、LN、PCⅢ、CⅣ的含量降低，大鼠肝组织胶原纤维增生程度减轻，细胞变性、坏死减少，TIMP-1表达减少。结论：HYSA具有抗大鼠肝纤维化的作用，其机制可能与减少TIMP-1的表达有关。

Objective： To study the effect of hydroxysafflor yellow A （HYSA） intervention in rats with hepatic fibrosis induced by GCl4. Methods： SD male rats were selected for this experiment. The rats were randomly divided into 5 groups： normal control group,model group, safflower group, HSYA group, colehicine group. Liver fibrosis model was made in all the rats by perfusion with carbon tetrachloride except normal control group. Appropriate drugs were intraperitoneally injected from the second week of modeling. The treatment lasted 8 weeks for all the groups. Serum hyaluronan （HA）, laminin （LN）, preeollagenⅢ （PCⅢ）, collagen Ⅳ （CⅣ） were detected by radioimmunity. Masson＇s triehrome staining of liver tissue was performed for histopathologieal evaluation of liver fibrosis. Hoechest 33342 fluorescent staining of liver tissue was performed to observe appearance of cell nucleus. The expression of tissue inhibitors of metalloproteinase 1 （TIMP-1） in liver tissue was detected by immunohistochemistry. Results： Compared with the model group, the levels of serum HA, LN, PCⅢ, CIV were significantly decreased in safflower group, HSYA group and eolehicine group. The apoptosis of liver cells was less and the level of fibrosis was reduced in the safflower group, HSYA group and eolchieine group. The expression intensity of TIMP-1 proteins was significantly lower in the safflower group, HSYA group and colehicine group. Conclusion： HYSA can prevent carbon tetrachloride-induced liver fibrosis in rats by reducing TIMP-1 synthesis.