N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸对大鼠肝纤维化模型跨膜信号转导的影响

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摘要目的观察N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸（AcSDKP）对胆总管结扎（BDL）所致大鼠肝纤维化的作用，探讨该作用与TGF-β1-Smad2/3及BMP-7-Smad1/5/8信号通路的关系。方法选取30只SD大鼠，随机分为假手术组、模型组、治疗组（AcSDKP），构建胆总管结扎肝纤维化模型，治疗组在造模的同时植入皮下微泵，给予AcSDKP治疗；第14天处死大鼠，采用ELISA酶联免疫法检测透明质酸（HA）和Ⅲ型胶原（PCⅢ）水平，采用羟脯氨酸（Hyp）测量法定量分析肝组织中总胶原蛋白的含量，采用Western印迹法检测肝组织中转化生长因子-β1（TGF-β1）、骨形成发生蛋白-7（BMP-7）、磷酸化Smad2/3、磷酸化Smad1/5/8蛋白的表达。结果与假手术组相比，模型组的血清HA、PCⅢ水平以及肝组织Hyp含量均明显升高（P＜0.05）。治疗组的血清HA、PCⅢ水平以及肝组织Hyp含量均较模型组显著下降，差异有统计学意义（P＜0.01）。模型组的肝组织内TGF-β1、磷酸化Smad2/3表达均高于假手术组，差异有统计学意义（P＜0.05）。治疗组的TGF-β1、磷酸化Smad2/3表达低于模型组，BMP-7、磷酸化Smad1/5/8表达高于模型组，差异有统计学意义（P＜0.05）。结论AcSDKP具有抑制大鼠BDL肝纤维化的作用，该作用可能与抑制TGF-β1通路，并激活BMP-7通路有关。

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	张蕾
	刘洪福
	吴雄健

关键词 ： N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸；TGF-&beta, 1；BMP-7；肝纤维化

Abstract：ObjectiveTo observe the effect of N-acetyl-seryl-aspartyl-lysyl-proline(AcSDKP)on rat liver fibrosis due to bile duct ligation (BDL),and to explore the relationship between this effect and TGF-β1-Smad2/3 and BMP-7-Smad1/5/8 signal channels.Methods30 SD rats were selected and randomly divided into the sham operation group,the model group and the treatment group(AcSDKP),BDL liver fibrosis model was built.when making model of the treatment group,subcutaneous micropump was implanted to provide AcSDKP treatment.On the 14thday,the rats were killed,then ELISA Enzyme linked immunosorbent assays were adopted to detect the hyaluronic acid(HA)and CollagenⅢ(PCⅢ) level,hydroxyproline(Hyp)measurement method was adopted to analyze the content of total collagen in hepatic tissue in a quantitative manner.Western blotting was adopted to detect the expression of transforming growth factor-β1(TGF-β1), bone morphogenetic protein-7(BMP-7),phosphorylation Smad2/3 and phosphorylation Smad1/5/8 protein in hepatic tissue.ResultsCompared with the sham operation group,the serum levels of HA,PCⅢ,and content of Hyp in hepatic tissue in the model group were increased(P＜0.05).The serum levels of HA,PCⅢ,and content of Hyp in hepatic tissue in the treatment group was significantly lower than that in the model group,with significant difference(P＜0.01).The expression of TGF-β1,phosphorylation Smad2/3 in the model group was higher than that in the sham operation group,with significant difference(P＜0.05).The expression of TGF-β1,phosphorylation Smad2/3 in the treatment group was lower than that in the model group,the expression of BMP-7 phosphorylation Smad1/5/8 in the treatment group was higher than that in the model group,with significant difference(P＜0.05).ConclusionAcSDKP has the effect of inhibiting BDL liver fibrosis in rats,which may be related to the inhibition of TGF-beta 1 pathway and activation of BMP-7 pathway.

Key words： N-acetyl-seryl-aspartyl-lysyl-proline Transforming growth factor-beta 1;Bone morphogenetic protein-7;Liver fibrosis

基金资助:江西省卫生计生委科技计划项目（20165342）；江西省赣州市指导性科技计划项目（GZ2014ZSF081）

引用本文:

张蕾;刘洪福;吴雄健. N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸对大鼠肝纤维化模型跨膜信号转导的影响[J]. 中国当代医药, 2016, 23(35): 4-6转14.
ZHANG Lei;LIU Hong-fu;WU Xiong-jian. Influence of N-acetyl-seryl-aspartyl-lysyl-proline on transmembrane signal transduction of rat liver fibrosis model. 中国当代医药, 2016, 23(35): 4-6转14.

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http://dangdaiyiyao.com/CN/ 或 http://dangdaiyiyao.com/CN/Y2016/V23/I35/4

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