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...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。展开更多
AIM:To investigate the protective effects of melatonin on carbon tetrachloride(CCl4)-induced hepatic fibrosis in experimental rats.METHODS:All rats were randomly divided into normal control group,model control group t...AIM:To investigate the protective effects of melatonin on carbon tetrachloride(CCl4)-induced hepatic fibrosis in experimental rats.METHODS:All rats were randomly divided into normal control group,model control group treated with CCl4 for 12 wk,CCl4+NAC group treated with CCl4+NAC(100 mg/kg,i.p.)for 12 wk,CCl4+MEL-1 group treated with CCl4+melatonin(2.5 mg/kg)for 12 wk,CCl4+MEL-2 group treated with CCl4+ melatonin(5.0 mg/kg)for 12 wk,and CCl4+MEL-3 group treated with CCl4+melatonin(10 mg/kg).Rats in the treatment groups were injected subcutaneously with sterile CCl4(3 mL/kg,body weight)in a ratio of 2:3 with olive oil twice a week.Rats in normal control group received hypodermic injection of olive oil at the same dose and frequency as those in treatment groups.At the end of experiment,rats in each group were anesthetized and sacrificed.Hematoxylin and eosin(HE)staining and Van Gieson staining were used to examine changes in liver pathology.Serum activities of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and protein concentration weremeasured with routine laboratory methods using an autoanalyzer.Hydroxyproline(HYP)content in liver and malondialdehyde(MDA)and glutathione peroxidase(GPx)levels in liver homogenates were assayed by spectrophotometry.Serum hyaluronic acid(HA),laminin(LN),and procollagenⅢN-terminal peptide(PⅢNP)were determined by radioimmunoassay.RESULTS:Pathologic grading showed that the fibrogenesis was much less severe in CCl4+MEL3 group than in model control group(u=2.172,P<0.05),indicating that melatonin(10 mg/kg)can significantly ameliorate CCl4-induced hepatic fibrotic changes.The serum levels of ALT and AST were markedly lower in CCl4+MEL treatment groups(5,10 mg/kg)than in model control group(ALT:286.23 ±121.91 U/L vs 201.15±101.16 U/L and 178.67 ±103.14 U/L,P=0.028,P=0.007;AST:431.00 ±166.35 U/L vs 321.23±162.48 U/L and 292.42 ±126.23 U/L,P=0.043,P=0.013).Similarly,the serum laminin(LN)and hyaluronic acid(HA)levels and hydroxyproline(HYP)contents in liver were signific展开更多
文摘目的: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。
基金Supported by The Natural Science Foundation of Anhui Province No.01043904the Natural Science Research Project of Colleges and Universities of Anhui Province No.KJ2007B146
文摘AIM:To investigate the protective effects of melatonin on carbon tetrachloride(CCl4)-induced hepatic fibrosis in experimental rats.METHODS:All rats were randomly divided into normal control group,model control group treated with CCl4 for 12 wk,CCl4+NAC group treated with CCl4+NAC(100 mg/kg,i.p.)for 12 wk,CCl4+MEL-1 group treated with CCl4+melatonin(2.5 mg/kg)for 12 wk,CCl4+MEL-2 group treated with CCl4+ melatonin(5.0 mg/kg)for 12 wk,and CCl4+MEL-3 group treated with CCl4+melatonin(10 mg/kg).Rats in the treatment groups were injected subcutaneously with sterile CCl4(3 mL/kg,body weight)in a ratio of 2:3 with olive oil twice a week.Rats in normal control group received hypodermic injection of olive oil at the same dose and frequency as those in treatment groups.At the end of experiment,rats in each group were anesthetized and sacrificed.Hematoxylin and eosin(HE)staining and Van Gieson staining were used to examine changes in liver pathology.Serum activities of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and protein concentration weremeasured with routine laboratory methods using an autoanalyzer.Hydroxyproline(HYP)content in liver and malondialdehyde(MDA)and glutathione peroxidase(GPx)levels in liver homogenates were assayed by spectrophotometry.Serum hyaluronic acid(HA),laminin(LN),and procollagenⅢN-terminal peptide(PⅢNP)were determined by radioimmunoassay.RESULTS:Pathologic grading showed that the fibrogenesis was much less severe in CCl4+MEL3 group than in model control group(u=2.172,P<0.05),indicating that melatonin(10 mg/kg)can significantly ameliorate CCl4-induced hepatic fibrotic changes.The serum levels of ALT and AST were markedly lower in CCl4+MEL treatment groups(5,10 mg/kg)than in model control group(ALT:286.23 ±121.91 U/L vs 201.15±101.16 U/L and 178.67 ±103.14 U/L,P=0.028,P=0.007;AST:431.00 ±166.35 U/L vs 321.23±162.48 U/L and 292.42 ±126.23 U/L,P=0.043,P=0.013).Similarly,the serum laminin(LN)and hyaluronic acid(HA)levels and hydroxyproline(HYP)contents in liver were signific
