【作者】 叶丽萍；

【导师】 张洪；

【作者基本信息】 武汉大学 ， 药剂学， 2005， 硕士

【摘要】 目的:研究枳棋子提取物对CCl₄诱导的实验性肝纤维化的预防及治疗作用。 方法:用CCl₄腹腔注射制备大鼠肝纤维化模型。预防实验中,分别取组织观察肝脏组织学及超微结构改变,免疫组化观察Ⅰ、Ⅲ型胶原蛋白及TGF-β₁的表达;治疗实验中,取组织测肝匀浆中的MDA含量、SOD活性,并取不同的时间点进行检测,从脂质过氧化指针和组织形态学方面进行动态观察。同时通过免疫组化观察Ⅰ、Ⅲ型胶原蛋白、TGF-β₁及TIMP-1的表达。 结果:预防组能减轻纤维化程度、肝细胞的变性坏死及炎性细胞浸润,使线粒体膜及脊恢复,减少内质网扩张,促进细胞再生,同时通过减少Ⅰ、Ⅲ型胶原含量及TGF-β₁的表达,阻滞纤维化的发生发展。治疗实验中,枳棋子能显著降低MDA含量、SOD活性及ColⅠ、Ⅲ、TGF-β₁、TIMP-1的表达,加速纤维化后的修复进程。 结论:当出现纤维化时应尽早去除损伤因素以便肝脏的自我恢复或在药物辅助下的恢复;枳棋子能够减少TGF-β₁分泌,降低TIMP-1的表达,促进胶原降解,保护肝细胞,阻滞肝纤维化的发生发展,促进纤维化逆转。其机理可能是通过加速HSC凋亡,减少ECM继续堆积,使TIMP-1下降,进一步降解已形成的纤维化性胶原,使肝纤维化逆转,而起到抗纤维化作用。更多还原

【Abstract】 Objective: To investigate the protective and therapeutic effect of Hovenia dulcis Thunb extract on carbon tetrachloride（CCl₄）-induced hepatic fibrosis in rats.Methods: CCl₄ was used to induce experimental liver fibrosis in Wistar Rats. In the protective study, liver pathological and untrastructure changes were studied. Immunohische- mistry was used to detect the expressions of collagen I, III and TGF- β₁. In the therapeutic study, the levels of MDA and SOD in liver homogenate were determined. The expressions of collagen I, III, TGF-β₁ and TIMP-1 were detected in tissue.Results: In prevented groups, the degeneration and necrosis of hepatic cells were in slight extent, fibroplasia was much less than the ones in the model groups, and pseudolobular partly disappeared. The expressions of collagen I, III and TGF- β₁ in prevented groups were significantly reduced（p<0.05）, compared to which in model groups. As in therapeutic groups, the levels of MDA and SOD in homogenate were much less than those in the model groups, and the expressions of collagen I &III, TGF-β₁ and TIMP-1 were predominantly reduced.Conclusions: Getting rid of the injury is most important in the therapy of fibrosis. Hovenia dulcis Thunb can reduce the severity of liver fibrosis in rats by depressing lipid peroxidation and the expression of TGF- β₁ and TIMP-1 significantly. The possible mechanism is to reduce hepatotoxic respones, anti-peroxidation of lipid, and stabilization of cell membrane, and probably by depressing the activation of HSC and improving the apoptosis of HSC. We found that in fibrosis the earlier we took measures, the better effect we would get. With the concentration of 15%, Hovenia dulcis Thunb would be the best for the therapy. The mechanism would accelerate the apoptosis of HSC, inhibit the deposition of ECM, and then accelerate the degradation of collagen.更多还原