虫草菌丝对大鼠实验性肝纤维化肝细胞增生的影响

Effect of Cordyceps sinensis on hepatocytic proliferation of experimental hepatic fibrosis in rats

目的:动态观察虫草菌丝对实验性肝纤维化肝细胞增生的影响,并探讨其可能的机制。 方法:设立模型对照组、虫草菌丝组和正常对照组。以CCL4和乙醇诱导大鼠肝纤维化模型,虫草菌丝组自造模10d后给予虫草菌丝悬浊液灌胃。正常对照组于实验开始时处死,虫草菌丝组和模型对照组分别于3,6,9wk末随机处死。取血及肝组织标本。应用HE染色观察肝组织形态学变化并评定肝细胞变性指数,生化方法测定血清白蛋白含量,免疫组化方法测定肝组织PCNA、HGF表达情况。 结果:与模型对照组相比,虫草菌丝组大鼠血清白蛋白含量在9wk时显著增高(27±0.7 vs 24±1 P<0.01),而3、6wk时无显著性差异。肝细胞变性指数仅在9wk时明显降低,但无统计学差异(P=0.0703)。肝组织PCNA阳性细胞数在3、6 wk时有不同程度的升高,其中6wk较为显著(29±10 vs 15±8 P<0.05)。而在9wk时显著下降(8±5 vs 28±18 P<0.05)。HGF强染率在3wk时显著增加(1.4±0.4 vs 0.7±0.3 P<0.05),6wk时无明显差异,9wk时显著下降(0.7±0.5 vs 1.8±1 P<0.01)。 结论:虫草菌丝通过上调HGF的表达,促进肝纤维化形成时期肝细胞再生,延缓慢性肝炎向肝硬化阶段发展的进程。

AIM: To dynamically Investigate the effect of Cordyceps slnensls (CS) on hepatocytlc proliferation In CCL4-plus ethanol-Induced hepatic fibrosls In rats.METHODS: Rats were randomly allocated Into a normal control group, a model control group and a CS group. The latter two groups were administered with CCL4, and ethanol solution to Induce hepatic fibrosls. The CS group was also treated with CS 10 days after the beginning of CCU and ethanol administration. Rats In normal control group were sacrificed at the beginning of experiment. Other two groups were sacrificed randomly at the end of the third, the sixth and the ninth week. Blood and tissue specimens were taken. Biochemical and immunohistochemical assays were used respectively to determine the hepatocyte degenerative Index (HDI), the level of albumin In serum and PCNA, HGF expression In liver tissue.RESULTS: Compared with model control group, serum albumin level in CS group was markedly elevated at the ninth week (27 ±0.7 vs 24 ± 1, P < 0. 01). No significant change was seen at the third and sixth weeks. Although no any significant statistical result (P = 0.0708), the HDI was obviously decreased at the ninth week. PCNA-positive cell count Increased at the third week, and, especially, the sixth week (29 ± 10 vs 15 ± 8, P< 0.05), and underwent dramatic drop at the ninth week (8 ± 5 vs 28 ± 18, P< 0.05). The up-regulation of HGF was only shown at the third week( 1.4 ± 0. 4 vs 0.7 ± 0.3, P< 0.05, with no significant change at the sixth week, and followed by a remarkable down-regulation at the ninth week (0.7±0.5 vs 1.8±1, P<0.01).CONCLUSION: Cordyceps sinensis can promote the hepatocytic proliferation in hepatic fibrosis and notably retard the development of cirrhosis by up-regulating HGF expression.