护肝解纤汤治疗肝纤维化及其作用机制的初步研究

目的 观察护肝解纤汤治疗大鼠肝纤维化效果及有关细胞因子的变化,初步探讨护肝解纤汤的作用机制.方法 100只雄性SD大鼠随机分组后,以四氯化碳腹腔内注射的方法建立大鼠肝纤维化模型,造模后施以由低、中、高剂量姜黄等组成的护肝解纤汤,以小柴胡汤和复方鳖甲软肝片为阳性对照.12周后处死大鼠,留取肝左叶同一部位新鲜肝组织,行苏木素-伊红、Masson染色,免疫组织化学染色检测肝组织Ⅰ、Ⅲ型胶原,转化生长因子β1(TGF β1)、血小板衍生长因子(PDGF-BB)的变化.多组数据间的比较采用SPSS12.0统计软件进行单因素方差分析.结果 护肝解纤汤能降低病理评分,改善肝纤维化病理损伤,抑制Ⅰ、Ⅲ型胶原合成并促使其降解,降低炎症因子TGF β1、PDGF-BB在肝组织的表达,正常组、模型对照组、低姜黄组、中姜黄组、高姜黄组、小柴胡汤组、复方鳖甲组肝组织TGF阳性面积百分比分别为7.56%±2.18%、29.25%±7.84%、13.54%±4.15%、21.82%±6.64%、20.06%±7.14%、13.78%±4.35%、12.75%±3.98%,P<0.05;PDGF-BB阳性百分比分别为1.68%±0.41%、11.70%±2.28%、3.65%±0.76%、5.24%±1.04%、6.37%±1.12%、4.16%±0.61%、3.38%±0.56%,P<0.05.上述作用以低姜黄组效果明显.结论 护肝解纤汤可改善大鼠肝纤维化的病理改变,降低Ⅰ型胶原、Ⅲ型胶原合成、减少PDGF-BB,TGF β1表达可能是其相关作用机制.

Preliminary study on mechanism of therapeutic effect of Huganjiexian decoction on hepatic fibrosis

Objective To observe the effects of Huganjiexian decoction on rat hepatic fibrosis and the screation of cytokines.Methods Rat hepatic fibrosis was induced by intraperitoneally injection of carbon tetrachloride.At the same time,these rats were treated with different dosages of Huganjiexian decoction.Sho-saiko-to compound treating group and Fufangbiejiarangan Tablets treating group were used as positive controls.After twelve weeks,all rats were executed.Histopathologic changes were observed after H.E and Masson stainings.The expression of collagen type Ⅰ,collagen type Ⅲ,TGF-beta 1 and PDGF-BB in liver were detected by immunohistochemical staining.Results Compared with fibrotic group,hepatic fibrosis in decoction groups was significantly improved.In decoction groups,levels of collagen type Ⅰ,collagen type Ⅲ,TGF β1 and PDGF-BB were decreased,especially in the low-dose curcumin group.The TGF-beta 1 positive percentage were 7.56%±2.18%,29.25%±7.84%,13.54%±4.15%,21.82%±6.64%,20.06%±7.14%,13.78%±4.35%,12.75%±3.98% in liver tissues from normal group,model group,low,middle,high curcumin,Sho-saiko-to compound and Fufangbiejiarangan Tablets treating groups respectively(P < 0.05);while the PDGF-BB positve percentage were 1.68%±0.41%,11.70%±2.28%,3.65%±0.76%,5.24%±1.04%,6.37%±1.12%,4.16%±0.61%,3.38%±0.56% in liver tissues from those groups respectively(P < 0.05).Conclusion Huganjiexian decoction can improve rat hepatic fibrosis,possibly via inhibiting the expression of collagen type Ⅰ,collagen type Ⅲ,TGF β1 and PDGF-BB.