双氢青蒿素对实验性小鼠肝纤维化的抑制作用

目的：探讨双氢青蒿素对胆总管结扎引起的小鼠肝纤维化的抑制作用及其作用机制。方法50只C57 BL-6小鼠随机分为假手术组（ n ＝10）、模型组（ n ＝20）和治疗组（ n ＝20）。模型组：采用胆总管结扎的方法建立小鼠肝纤维化模型；治疗组：在胆总管结扎术后第3周开始以20μg／g的双氢青蒿素灌胃，1次／d，共12次。假手术组：只是分离出胆总管，置线不结扎并缝合腹腔后第3周开始以等剂量的DMSO 0．9％氯化钠溶液灌胃，1次／d，共12次。3组的肝组织切片经HE和天狼猩红染色法观察其组织学病理变化；Western blot方法检测Ⅰ型胶原和α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA）蛋白的表达水平。结果经HE和天狼星红染色法结果证实小鼠肝纤维化动物模型的成功建立。模型组小鼠肝内出现灶状坏死，汇管区纤维组织和胆总管明显增生，肝组织中Ⅰ型胶原蛋白和α-SMA含量增加，与假手术组相比其差异有统计学意义（ P ＜0．05）。治疗组经过双氢青蒿素治疗后，小鼠肝内纤维组织增生降低，肝组织中Ⅰ型胶原蛋白和α-SMA含量降低，与模型组比较差异有统计学意义（ P ＜0．05）。结论双氢青蒿素具有抗肝组织纤维化作用，提示可作为一种新型抗肝组织纤维化药物。

The inhibitory efefcts of dihydroartemisinin on liver fibrosis in experiment al mice

Objective To investigate the inhibitory effects and action mechanism of dihydroartemisinin ( DHA) on liver fibrosis induced by bile duct ligation in experimental mice .Methods Fifty C57BL-6 mice were randomly divided into sham-operation group ( n =10),model group ( n =20) and treatment group ( n =20).The animal models with hepatic fibrosis were established by bile duct ligation ,then,on the third week after bile duct ligation , the mice in treatment group were given DHA 20μg/g by gavage,once a day for 12 days.However the mice in sham-operation group were given equal dose of DMSO physiological saline by gavage , once a day for 12 days.The histopathological changes were observed by HE and sirius red staining for three groups ,moreover , the expression levels of typeⅠcollagen and α-smooth muscle actin (α-SMA ) were detected by Western Blot .Results The results by HE and sirius red staining demonstrated that the animal models with hepatic fibrosis were successfully established in experimental mice .The focal cellular necrosis and fibrous tissue hyperplasia were found in liver of mice of model group , furthermore , the expression levels of type I collagen and α-SMA were obviously increased,there were significant differences between model group and sham -operation group ( P <0.05).After treatment by DHA in treatment group ,the fibrous tissue hyperplasia in liver was improved and the expression levels of type I collagen andα-SMA were significantly decreased , as compared with those in model group ( P<0.05).Conclusion DHA has the effects of anti-fibrosis of liver tissues, thus, it suggests that DHA can be regarded as a potential therapeutic drug for liver fibrosis .