中文摘要：

目的探讨氧化苦参碱（oxymatrine,OM）减轻四氯化碳诱导肝纤维化（hepatic fibrosis,HF）的机制。方法建立四氯化碳诱导的大鼠HF模型,制备氧化苦参碱脂质体（Oxymatrine liposomes,OM-liposome）、精氨酸-甘氨酸-天冬氨酸（Arginine-Glycin-Aspartic acid,RGD）三肽序列偶联的OM及异硫氰酸荧光素（fluorescent isothiocyanate,FITC）标记的OM-liposome和RGD-OM-liposome。分离HF大鼠的肝脏星状细胞（hepatic stellate cells,HSCs）并体外培养：①将OM-liposome、RGD-OM-liposome和RGD偶联的空白脂质体（RGD-liposome）作用于HSCs,利用透射电镜检测HSCs的细胞亚显微结构（凋亡小体）变化,利用流式细胞技术检测HSCs的细胞周期,利用台盼蓝染色检测HSCs的细胞活性。②将FITC-OM-liposome和FITC-RGD-OM-liposome作用于HSCs,利用荧光显微镜技术比较两种剂型OM在HSCs中的分布。结果①与RGD-liposome比较,OM-liposome可促进HSCs凋亡小体形成,增加HSCs凋亡,降低HSCs的细胞活性;与OM-liposome比较,RGD-OM-liposome可进一步增加HSCs内凋亡小体,促进HSCs凋亡,降低HSCs活性。②RGD可促进OM-liposome在HSCs内的分布。结论 OM-liposome可在体外诱导HSCs凋亡,RGD可促进OM-liposome在HSCs的分布,进一步促进HSCs的凋亡。诱导HSCs凋亡可能是OM减轻肝纤维化的重要机制。

英文摘要：

Objective To explore the mechanism of oxymatrine（OM） for reduction of hepatic fibrosis（HF） induced by tetrachloromethane.Methods HF rat model induced by tetrachloromethane was established.Oxymatrine liposome（OM-liposome）,Arginine-Glycin-Aspartic acid（RGD） loading OM-liposome,marked OM-liposome and RGD-OM-liposome by fluorescent isothiocyanate（FITC） were prepared.Hepatic stellate cells（HSCs） from HF rats were isolated and cultured in vivo.①OM-liposome,RGD-OM-liposome and RGD-liposome were acted on HSCs,then changes of cellular submicroscopic structure of HSCs（apoptotic body） were observed by transmission electron microscope.Cell cycles of HSCs were detected by flow cytometry,and its activity was examined by placenta blue staining.②FITC-OM-liposome and FITC-RGD-OM-liposom were acted on HSCs,then the distributions of the two-types OM in HSCs were compared by fluorescent microscopy.Results ①Compared with RGD-liposome,OM-liposome could promote the production of apoptotic bodies in HSCs,increase its apoptosis,and lower its activity.Compared with OM-liposome,RGD-OM-liposome might further increase numbers of apoptotic bodies in HSCs,enhance its apoptosis,and lower its activity.②RGD could promote the distribution of OM-liposome in HSCs.Conclusion OM-liposome can induce the apoptosis of HSCs in vivo.RGD plays a role in promoting distribution of OM-liposome in HSCs,and further facilitating its apoptosis.Inducing apoptosis of HSCs may be an important mechanism to explain OM reduction of HF.