柔肝煎抗肝纤维化作用及其对大鼠肝组织TGF-β_1和Smads的影响
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摘要
目的：客观评价柔肝煎对于实验大鼠肝纤维化的防治作用；通过对于肝组织TGF-β1和Smads表达的研究,探索柔肝煎抗肝纤维化可能的机制。
方法：健康雄性SD大鼠105只,体重200g±20g,共分为7组,即正常组、模型组、秋水仙碱组、扶正化瘀胶囊组和柔肝冲剂高、中、低剂量组,每组15只。采用CCL4法诱导大鼠肝纤维化模型,用高、中、低剂量的柔肝煎,以及秋水仙碱和扶正化瘀胶囊进行干预治疗,实验周期为12周。实验结束后进行对大鼠的一般状态进行评估,并提取相关标本进行肝功能(AST.ALT.PH.TP).肝纤维化指标(HA、LN、C-Ⅳ、 PCⅢ)、肝组织学、以及肝组织中TGF-β1、Smad3、Smad7表达等的检测。
结果：各治疗组大鼠的一般状态都较空白组差,但好于模型组,而柔肝煎高、中、低剂量组的之间并没有明显差异。正常组没有肝纤维化的发生,而模型组大鼠则全部发生了肝纤维化,而且肝纤维化的程度也是最严重。其余5组的肝纤维化发生的程度和数量并没有明显的差异,P>0.05。与正常组比较各组血清AST.ALT和PH明显升高,而TP变化较小；但与模型组相比,各治疗组血清肝功能明显减轻,P<0.01,并且之间的变化差异并不显著,P>0.05。肝纤维化指标方面,各组指标均较空白组升高,而各治疗组指标明显低于模型组,P<0.01,柔肝煎高、中、低剂量组与秋水仙碱组、扶正化瘀胶囊组比较无显著性差异,P>0.05。正常组大鼠肝组织中TGF-β1和Smad3的含量都明显的低于模型组和各个治疗组,且有显著性的差异,P<0.01或P<0.05；并且模型组大鼠肝组织中TGF-β1和Smad3的含量则是7组中最高的,差异显著,具有统计学意义,P<0.05。而各个治疗组中,二者的表达并没有显著性差异,P>0.05；Smad7在正常组和模型组中的含量无显著性差异,P>0.05。而正常组和模型组与各个治疗组间的比较差异性显著,P<0.01；但是各个治疗组间的比较并无显著性差异(P>0.05)。
结论：1.柔肝煎能够有效地改善由四氯化碳诱导的肝纤维化大鼠的肝脏功能(ALT、AST、PH、TP),并能够降低实验性肝纤维化大鼠血清的肝纤维化四项指标(HA、LN、IV-C、PCⅢ)。2.柔肝煎能够有效地改善由四氯化碳诱导的肝纤维化大鼠的肝组织的病理变化,减少纤维组织的增生。3.柔肝煎能够减少由四氯化碳诱导的肝纤维化大鼠的肝组织中TGF-β1的表达。这可能是柔肝煎防治肝纤维化的作用机制之一。4.尽管同时有Smad3表达的抑制和Smad7表达的增加,仍无法确定柔肝煎对于肝纤维化时肝TGF-β1/Smad3信号转导通路的干预作用。5.柔肝煎各剂量组之间的疗效并没有明显差异。
Objective To evaluate the control effect of Rouganjian on liver fibrosis in rats, and the change of TGF-β1and Smads in liver of. To explore the mechanism of Rouganjian Decoction on liver fibrosis.
Methods105male SD rats with200g±20g in weight were randomly divided into blank control group, model control group, colchicines group, fuzhenghuayu group, high dosage group,middle doseage group and low dosage group of rouganjian,15in every group. Using the CCL4composite approach to make the rat modle. The course of treat-ment was12weeks.After treatment,All the rats was killed,and the materials and blood was taken,and to detect AST, ALT, PH,TP, HA, LN, C-Ⅳ, PC Ⅲ after eight weeks. Investigating the variation of liver histology, Hestain and Masson trichrome stain. Meanwhile detecting TGF-β1and protein expression of Smad3, Smad7by immune-histochemical method.
Result The general condition of rats in all treatment groups are worse than the blank group, but better than the model group, and there was no significant difference between Rouganjian high, medium, low dose group. The normal group without hepatic fibrosis, and the rats in the model group were all occurred in liver fibrosis, and liver fibrosis is the most serious. There is no significant difference between hepatic fibrosis degree and the quantity of the remaining5group, P>0.05. Compared with the normal group, the serum concentrations of AST, ALT and PH increased significantly, while TP changes little; but compared with the model group, the treatment group significantly reduced serum liver function, P<0.01, the difference between change and is not significant, P>0.05. Liver fibrosis indexes, each index all increased compared with control group, the treatment group was lower than that of model group, P<0.01, there was no significant difference between Rouganjian Decoction high, medium, low dose group and colchicine group, Fuzheng Huayu capsule group, P>0.05. In normal rat liver tissue of TGF-β1 and Smad3were significantly lower in model group and each treatment group, and there were significant differences, P<0.01or P<0.05; and the content of liver tissue in model rats of TGF-β1and Smad3, Smad7in the group the highest, difference signi-ficantly, with statistical significance, P<0.05.Each treatment groups, and no significant difference in expression of the two, P>0.05; there was no significant difference of Smad7in normal group and model group in the content, P>0.05.While the normal group and model group and all treatment groups significantly, P<0.01; but there is no comparison between the treatment group was signi-ficant difference, P>0.05.
Conclusion1.Rouganjian can effectively improve liver fibrosis rats induced by CC14liver function (ALT, AST, PH, TP), and can decrease the level of serum in experimental hepatic fibrosis rat hepatic fibrosis and four indexes (HA, LN, Ⅳ-C, PC Ⅲ).2.Patho-logical changes of hepatic tissue Rouganjian decoction can ef-fectively improve liver fibrosis rats induced by CC14reduction of, fibrous tissue hyperplasia.3.Rouganjian decoction can reduce the expression of TGF-β1in liver tissue of hepatic fibrosis rats induced by CC14in. This may be one of the mechanisms of Rouganjian Decoction in prevention and treatment of liver fibrosis.4.Even though both increased expression and Smad7Smad3expression, is still unable to determine Rouganjian Decoction for the intervention of liver TGF-β1/Smad3signal transduction pathway in liver fibrosis.5.No significant difference of efficacy between Rouganjian Decoction dose groups.
方法：健康雄性SD大鼠105只,体重200g±20g,共分为7组,即正常组、模型组、秋水仙碱组、扶正化瘀胶囊组和柔肝冲剂高、中、低剂量组,每组15只。采用CCL4法诱导大鼠肝纤维化模型,用高、中、低剂量的柔肝煎,以及秋水仙碱和扶正化瘀胶囊进行干预治疗,实验周期为12周。实验结束后进行对大鼠的一般状态进行评估,并提取相关标本进行肝功能(AST.ALT.PH.TP).肝纤维化指标(HA、LN、C-Ⅳ、 PCⅢ)、肝组织学、以及肝组织中TGF-β1、Smad3、Smad7表达等的检测。
结果：各治疗组大鼠的一般状态都较空白组差,但好于模型组,而柔肝煎高、中、低剂量组的之间并没有明显差异。正常组没有肝纤维化的发生,而模型组大鼠则全部发生了肝纤维化,而且肝纤维化的程度也是最严重。其余5组的肝纤维化发生的程度和数量并没有明显的差异,P>0.05。与正常组比较各组血清AST.ALT和PH明显升高,而TP变化较小；但与模型组相比,各治疗组血清肝功能明显减轻,P<0.01,并且之间的变化差异并不显著,P>0.05。肝纤维化指标方面,各组指标均较空白组升高,而各治疗组指标明显低于模型组,P<0.01,柔肝煎高、中、低剂量组与秋水仙碱组、扶正化瘀胶囊组比较无显著性差异,P>0.05。正常组大鼠肝组织中TGF-β1和Smad3的含量都明显的低于模型组和各个治疗组,且有显著性的差异,P<0.01或P<0.05；并且模型组大鼠肝组织中TGF-β1和Smad3的含量则是7组中最高的,差异显著,具有统计学意义,P<0.05。而各个治疗组中,二者的表达并没有显著性差异,P>0.05；Smad7在正常组和模型组中的含量无显著性差异,P>0.05。而正常组和模型组与各个治疗组间的比较差异性显著,P<0.01；但是各个治疗组间的比较并无显著性差异(P>0.05)。
结论：1.柔肝煎能够有效地改善由四氯化碳诱导的肝纤维化大鼠的肝脏功能(ALT、AST、PH、TP),并能够降低实验性肝纤维化大鼠血清的肝纤维化四项指标(HA、LN、IV-C、PCⅢ)。2.柔肝煎能够有效地改善由四氯化碳诱导的肝纤维化大鼠的肝组织的病理变化,减少纤维组织的增生。3.柔肝煎能够减少由四氯化碳诱导的肝纤维化大鼠的肝组织中TGF-β1的表达。这可能是柔肝煎防治肝纤维化的作用机制之一。4.尽管同时有Smad3表达的抑制和Smad7表达的增加,仍无法确定柔肝煎对于肝纤维化时肝TGF-β1/Smad3信号转导通路的干预作用。5.柔肝煎各剂量组之间的疗效并没有明显差异。
Objective To evaluate the control effect of Rouganjian on liver fibrosis in rats, and the change of TGF-β1and Smads in liver of. To explore the mechanism of Rouganjian Decoction on liver fibrosis.
Methods105male SD rats with200g±20g in weight were randomly divided into blank control group, model control group, colchicines group, fuzhenghuayu group, high dosage group,middle doseage group and low dosage group of rouganjian,15in every group. Using the CCL4composite approach to make the rat modle. The course of treat-ment was12weeks.After treatment,All the rats was killed,and the materials and blood was taken,and to detect AST, ALT, PH,TP, HA, LN, C-Ⅳ, PC Ⅲ after eight weeks. Investigating the variation of liver histology, Hestain and Masson trichrome stain. Meanwhile detecting TGF-β1and protein expression of Smad3, Smad7by immune-histochemical method.
Result The general condition of rats in all treatment groups are worse than the blank group, but better than the model group, and there was no significant difference between Rouganjian high, medium, low dose group. The normal group without hepatic fibrosis, and the rats in the model group were all occurred in liver fibrosis, and liver fibrosis is the most serious. There is no significant difference between hepatic fibrosis degree and the quantity of the remaining5group, P>0.05. Compared with the normal group, the serum concentrations of AST, ALT and PH increased significantly, while TP changes little; but compared with the model group, the treatment group significantly reduced serum liver function, P<0.01, the difference between change and is not significant, P>0.05. Liver fibrosis indexes, each index all increased compared with control group, the treatment group was lower than that of model group, P<0.01, there was no significant difference between Rouganjian Decoction high, medium, low dose group and colchicine group, Fuzheng Huayu capsule group, P>0.05. In normal rat liver tissue of TGF-β1 and Smad3were significantly lower in model group and each treatment group, and there were significant differences, P<0.01or P<0.05; and the content of liver tissue in model rats of TGF-β1and Smad3, Smad7in the group the highest, difference signi-ficantly, with statistical significance, P<0.05.Each treatment groups, and no significant difference in expression of the two, P>0.05; there was no significant difference of Smad7in normal group and model group in the content, P>0.05.While the normal group and model group and all treatment groups significantly, P<0.01; but there is no comparison between the treatment group was signi-ficant difference, P>0.05.
Conclusion1.Rouganjian can effectively improve liver fibrosis rats induced by CC14liver function (ALT, AST, PH, TP), and can decrease the level of serum in experimental hepatic fibrosis rat hepatic fibrosis and four indexes (HA, LN, Ⅳ-C, PC Ⅲ).2.Patho-logical changes of hepatic tissue Rouganjian decoction can ef-fectively improve liver fibrosis rats induced by CC14reduction of, fibrous tissue hyperplasia.3.Rouganjian decoction can reduce the expression of TGF-β1in liver tissue of hepatic fibrosis rats induced by CC14in. This may be one of the mechanisms of Rouganjian Decoction in prevention and treatment of liver fibrosis.4.Even though both increased expression and Smad7Smad3expression, is still unable to determine Rouganjian Decoction for the intervention of liver TGF-β1/Smad3signal transduction pathway in liver fibrosis.5.No significant difference of efficacy between Rouganjian Decoction dose groups.
引文
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