一贯煎对CCl_4诱导的肝纤维化大鼠肝组织胶原代谢的影响

目的：探讨一贯煎对四氯化碳（carbon tetrachloride,CCl4）诱导的肝纤维化大鼠肝脏胶原代谢的影响。方法：腹腔注射CCl49周制备大鼠肝纤维化模型,于造模第3周、第6周末各处死6只大鼠作动态观察,自第7周起将模型大鼠随机分为模型对照组和干预组。干预组于继续造模的同时给予一贯煎灌胃3周,正常组与模型对照组大鼠给予同体积蒸馏水灌胃。第9周末处死全部大鼠,采集肝组织标本,检测肝组织组织金属蛋白酶抑制剂1（tissue inhibitor ofmetalloproteinase-1,TI MP-1）、-2,基质金属蛋白酶13（matrix metalloproteinase-13,MMP-13）、-14,α平滑肌肌动蛋白（α-smooth muscle actin,α-SMA）,Ⅰ型胶原（collagen typeⅠ,ColⅠ）等的蛋白表达以及MMP-2、-9的活性。结果：与正常大鼠比较,造模第3、6和9周时肝纤维化大鼠肝组织胶原纤维增生程度增加,肝组织α-SMA、ColⅠ、TI MP-1、TI MP-2、MMP-13、MMP-14蛋白表达和MMP-2、MMP-9活性逐渐升高（P〈0.05或P〈0.01）;与9周模型组比较,一贯煎组大鼠胶原纤维增生程度显著减轻（P〈0.05）,肝组织α-SMA、ColⅠ、TI MP-1、TI MP-2、MMP-13和MMP-14蛋白表达及MMP-2、MMP-9活性显著降低（P〈0.01）。结论：一贯煎可以抑制肝星状细胞活化,抑制胶原的合成,促进过度增生的胶原纤维的降解,从而抑制CCl4诱导大鼠肝硬化的形成。

Effects of Chinese herbal medicine Yiguanjian Decoction on collagen metabolism of hepatic tissues in rats with CCl4-induced liver fibrosis

Objective：To investigate the effects of Yiguanjian Decoction,a compound traditional Chinese herbal medicine,on collagen metabolism of hepatic tissues in rats with carbon tetrachloride（CCl4）-induced liver fibrosis.Methods：Liver fibrosis was induced in rats by intraperitoneal injection of 50% CCl4-olive oil solution at a dose of 1 mL/kg body weight,twice per week for 9 consecutive weeks.Six rats were sacrificed for dynamic observation at the end of the 3rd and 6th week respectively,and the other rats were divided into 9-week untreated group and Yiguanjian Decoction group which was given Yiguanjian Decoction intragastrically in the subsequent 3-week modeling period.Another 6 rats were used as normal group.Rats in the normal group and 9-week untreated group were treated with distilled water.At the end of the 9th week,all rats were sacrificed,and their blood serum and liver tissue were collected for measuring hepatic histology and expressions of α-smooth muscle actin（α-SMA）,tissue inhibitor of metalloproteinase（TIMP）-1,TIMP-2,matrix metalloproteinase（MMP）-13,MMP-14,collagen type Ⅰ（ColⅠ）,and activities of MMP-2 and-9.Results：Compared with the normal group,collagen fiber deposition,expressions of α-SMA,ColⅠ,TIMP-1,TIMP-2,MMP-13 and MMP-14 and activities of MMP-2 and-9 in the liver tissues gradually increased in the untreated group（P0.05,P0.01）.These changes were significantly suppressed by Yiguanjian Decoction.Conclusion：Yiguanjian Decoction exerts inhibition on formation of CCl4-induced cirrhosis in rats.The therapeutic mechanism may be related to inhibiting hepatic stellate cell activation,collagen secretion,and promoting collagen fiber degradation.