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目的观察水飞蓟宾(silybinin)在大鼠实验性肝纤维化过程中抗肝维化作用及其可能的机制。方法雌性Wistar大鼠70只,随机分为正常对照组(n=5)、纤维化模型组(n=33)和水飞蓟宾治疗组(n=32),后两组各自再随机分为1周、2周、4周、6周组。纤维化模型组以CCl4造成化学性肝损伤;水飞蓟宾治疗组注射CCl4的同时以水飞蓟宾50mg/(kg·d)灌胃。各组动物(也包括正常对照组)按设计分别于给药后1周、2周、4周、6周末,在乙醚麻醉、无菌无热源条件下,行腹主动脉采血和肝组织取材进行病理学观察。用Western-blot和原位杂交方法检测各组肝脏结缔组织生长因子(CTGF)的表达;测定各组血浆内毒素(ET)含量,同时也测定羟脯氨酸(Hyp)、丙二醛(MDA)、丙氨酸氨基转移酶(ALT)的水平。结果与正常对照组比较,纤维化模型组和水飞蓟宾治疗组各项指标均有显著升高,且ET含量升高先于CTGF;与纤维化模型组比较,水飞蓟宾治疗组肝脏病理学损伤性改变有明显的减轻,血浆ET、ALT水平以及肝组织MDA、Hyp含量均有显著的降低,CTGF表达也明显的下调。结论水飞蓟宾可有效地改善实验性肝纤维化程度,其机制可能与其降低肠源性内毒素血症、下调CTGF的表达有关。
Objective To observe the effect of silybinin on liver fibrosis and its possible mechanism during experimental hepatic fibrosis in rats. Methods Seventy female Wistar rats were randomly divided into normal control group (n = 5), fibrosis model group (n = 33) and silybin treatment group (n = 32) 1 week, 2 weeks, 4 weeks, 6 weeks group. In the fibrosis model group, chemical liver injury was caused by CCl4; while in silibinin treatment group, CCl4 was injected intragastrically at a dose of 50 mg / (kg · d). Each group of animals (including the normal control group) was designed according to the design after 1, 2 weeks, 4 weeks, 6 weeks after administration, respectively, under ether anesthesia, aseptic and pyrogen-free conditions, abdominal aorta blood and liver tissue taken Pathological observation. The expression of connective tissue growth factor (CTGF) in each group was detected by Western-blot and in situ hybridization. The levels of plasma endotoxin (ET) in each group were also measured. The levels of hydroxyproline (Hyp), malondialdehyde (MDA) ), Alanine aminotransferase (ALT) levels. Results Compared with the normal control group, the indexes of fibrosis model group and silybin treatment group were significantly increased, and the ET content increased before CTGF; compared with the fibrosis model group, the silybin treatment group Pathological damage was significantly reduced, plasma ET, ALT levels and liver MDA and Hyp levels were significantly reduced, CTGF expression was significantly down-regulated. Conclusion Silybin can effectively improve the degree of experimental hepatic fibrosis, and its mechanism may be related to reducing intestinal endotoxemia and down-regulating the expression of CTGF.