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纸质出版日期:2017
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戴琦, 罗勇兵, 李梦乔, 等. 益气活血利水汤对肝纤维化模型大鼠Necdin-Wnt信号通路的影响[J]. 中国实验方剂学杂志, 2017,23(7):134-140.
DAI Qi, LUO Yong-bing, LI Meng-qiao, et al. Effect of Yiqi Huoxue Lishui Decoction on Necdin-Wnt Signal Pathway in Rats with Hepatic Fibrosis[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(7): 134-140.
戴琦, 罗勇兵, 李梦乔, 等. 益气活血利水汤对肝纤维化模型大鼠Necdin-Wnt信号通路的影响[J]. 中国实验方剂学杂志, 2017,23(7):134-140. DOI: 10.13422/j.cnki.syfjx.2017070134.
DAI Qi, LUO Yong-bing, LI Meng-qiao, et al. Effect of Yiqi Huoxue Lishui Decoction on Necdin-Wnt Signal Pathway in Rats with Hepatic Fibrosis[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(7): 134-140. DOI: 10.13422/j.cnki.syfjx.2017070134.
目的:观察益气活血利水汤对肝纤维化模型大鼠necdin-Wnt信号通路的影响,探讨益气活血利水汤抗肝纤维化的作用机制。方法: 60只SD大鼠中随机抽取12只为正常组,造模成功的45只大鼠随机分为益气活血利水汤(9.6 g·kg-1)组(n=12),益气活血利水汤(14.4 g·kg-1)组(n=11),秋水仙碱组(Col组,n=11)和模型组(n=11)。正常组和模型组灌胃(ig)生理盐水,益气活血利水汤组ig益气活血利水汤9.6,14.4 g·kg-1·d-1,Col组ig Col 0.1 mg·kg-1·d-1。10周后观察两组的血清透明质酸(hyaluronan acid,HA),层黏蛋白(laminin,LN),Ⅲ型前胶原(type Ⅲ procollagen,PCⅢ),Ⅳ型胶原(type Ⅳ collagen,CⅣ)水平;苏木精-伊红(HE)染色观察其病理表现,Masson染色观察胶原蛋白变化,观察各组necdin,β-链蛋白(β-catenin),过氧化物增殖激活受体(PPARγ)蛋白和mRNA表达水平。结果:与正常组比较,模型组大鼠血清HA,LN,PCⅢ,CⅣ水平,纤维化分期的标准(Metavir)评分,胶原纤维含量,necdin,β-catenin蛋白及mRNA表达显著升高(P<0.01);与模型组比较,Col组HA,LN,PCⅢ,CⅣ水平,METAVIR评分,胶原纤维含量,necdin,β-catenin蛋白及mRNA表达显著降低(P<0.01);与Col组比较,益气活血利水汤(9.6 g·kg-1)组HA,LN,PCⅢ,CⅣ水平,METAVIR评分,胶原纤维含量,necdin,β-catenin蛋白及mRNA表达显著降低(P<0.01);与益气活血利水汤(9.6 g·kg-1)组比较,益气活血利水汤(14.4 g·kg-1)组HA,LN,PCⅢ,CⅣ水平,Metavir评分,胶原纤维含量,necdin,β-catenin蛋白及mRNA表达显著降低(P<0.01)。与正常组比较,模型组PPARγ蛋白及mRNA表达显著降低(P<0.01);与模型组比较,Col组PPARγ蛋白及mRNA表达显著升高(P<0.01);与益气活血利水汤(9.6 g·kg-1)组比较,益气活血利水汤(14.4 g·kg-1)组PPARγ蛋白及mRNA表达明显升高(P<0.05,P<0.01)。结论:益气活血利水汤可抑制necdin-Wnt/β-catenin通路的活性,解除Wnt/β-catenin对PPARγ的抑制,具有抗肝纤维化的效果。
Objective: To observe the effect of Yiqi Huoxue Lishui decoction on necdin-Wnt signal pathway in rats with hepatic fibrosis
and explore its mechanismin treating hepatic fibrosis. Method: The 12 SD rats were selected from 60 SD rats as normal group
and 45 successfully modeled SD rats were randomly divided into Yiqi Huoxue Lishui decoction standard dose group(standard group
n=12)
Yiqi Huoxue Lishui decoction high dose group(high dose group
n=11)
colchicine group (Col group
n=11) and model group(n=11). The rats innormal group and model group received intragastric administration of normal saline
rats in standard group received intragastric administration of 9.6 g·kg-1·d-1Yiqi Huoxue Lishui decoction
rats in high dose group received intragastric administration of 14.4 g·kg-1·d-1Yiqi Huoxue Lishui decoction
and the rats in Col group received intragastric administration of 0.1 mg·kg-1·d-1colchicine. After ten weeks
the level of hyaluronic acid (HA)
laminin (LN)
type Ⅲ Procollagen(PC Ⅲ)
and type Ⅳ collagen (C Ⅳ) in serum were observed in all the groups.Hematoxylin-eosin staining(HE) was used to observe their pathologic manifestation
and Masson staining was used to observe the collagen changes.The protein and mRNA expression levels of necdin
β-catenin
and peroxisome proliferator activated receptor γ(PPARγ) were observed. Result: As compared with the normal group
the levels of HA
LN
PCⅢ and CⅣ in serum
Metavir scores in fibrosis stage
content of collagen fibers
levels of necdin and β-catenin protein and mRNA expression levels were significantly higher in model group (P<0.01). As compared with the model group
the levels of HA
LN
PCⅢ and CⅣ
Metavir scores
content of collagen fibers
levels of necdin and β-catenin proteinand mRNA expression levels of necdin and β-catenin in Col group were significantly lower (P<0.01). As compared with the Col group
the levels of HA
LN
PCⅢ and CⅣ
Metavir scores
content of collagen fibers
levelsof necdin and β-catenin protein and mRNA expression levels were significantly lower in standard group(P<0.01). As compared with standard group
the levels of HA
LN
PCⅢ and CⅣ
Metavir scores
content of collagen fibers
levels of necdin and β-catenin protein and mRNA expression levels were significantly lower in high dose group(P<0.05
P<0.01). As compared with normal group
the PPARγ protein and mRNA expression levels were significantly lower in model group (P<0.01). As compared with the model group
the PPARγ protein and mRNA expression levels were significantly higher in Col group(P<0.01). As compared with Col group
the PPARγ protein and mRNA expression levels were significantly higher in standard group(P<0.01). As compared with the standard group
the PPARγ protein and mRNA expression levels were significantly higher in high dose group(P<0.05
P<0.01). Conclusion: The Yiqi Huoxue Lishui decoction can inhibit the activity of necdin-Wnt/β-catenin pathway
relieve the inhibition of Wnt/β-catenin on PPARγ
and have the effect of antihepatic fibrosis.
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