N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸对大鼠心脏成纤维细胞c-Jun氨基末端激酶通路活化的影响
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中华人民共和国人事部留学人员科技活动项目(国人厅发[2006]164号);;河北省科技厅博士基金项目(04547002D-5);;唐山市新药基础研究重点实验室项目(04362001B-9)


Effect of AcSDKP on the Activation of C-Jun N-Terminal Kinase Induced by PDGF in Cultured Rat Cardiac Fibroblasts
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    摘要:

    目的探讨N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(AcSDKP)对血小板源生长因子诱导的大鼠心脏成纤维细胞增殖及胶原合成以及c-Jun氨基末端激酶表达的影响。方法选用新生Wistar大鼠心脏成纤维细胞作为实验研究材料,MTT法检测心脏成纤维细胞代谢活性的改变,免疫细胞化学法检测Ⅰ型、Ⅲ型胶原表达的改变,Western Blotting检测大鼠心脏成纤维细胞中磷酸化JNK(p-JNK)和JNK蛋白及Ⅰ型、Ⅲ型胶原蛋白的表达。结果10μg/L血小板源生长因子刺激下,代表大鼠心脏成纤维细胞代谢活性的OD值增加,Ⅰ型、Ⅲ型胶原表达增强,表明血小板源生长因子刺激了心脏成纤维细胞增殖,促进了胶原的合成。同时p-JNK蛋白表达增高,而JNK蛋白表达无明显改变。10-9mol/LAcSDKP能够抑制血小板源生长因子诱导的大鼠心脏成纤维细胞代谢活性,同时抑制了Ⅰ型、Ⅲ型胶原及p-JNK蛋白的表达,而JNK蛋白表达无明显改变。结论AcSDKP能够通过阻断血小板源生长因子介导的JNK通路激活进而抑制大鼠心脏成纤维细胞增殖和胶原蛋白表达。

    Abstract:

    Aim To investigate the effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on platelet-derived growth factor (PDGF)-induced cardiac fibroblast proliferation and collagen synthesis,and the expression of JNK. Methods Neonatal rat cardiac fibroblasts were used in the experiment,the proliferation of cardiac fibroblasts was observed by MTT assay,the expression of typeⅠand type Ⅲ collagen protein in cardiac fibroblasts was detected by immunocytochemistry assay. The expression of JNK protein,phosphorylation of JNK protein and typeⅠand type Ⅲ collagen protein in cardiac fibroblasts was measured by Western Blotting analysis. Results 10 μg/L PDGF increased cell metabolic activity,expression of type Ⅰ and type Ⅲ collagen and phosphorylation of JNK,while the protein levels of JNK were not changed. 10-9 mol/L AcSDKP could inhibit cardiac fibroblasts proliferation,expression of type Ⅰ and type Ⅲ collagen and phosphorylation of JNK mediated by PDGF,while the protein levels of JNK were not significantly changed. Conclusion AcSDKP could inhibit the proliferation and collagen synthesis of cardiac fibroblasts induced by PDGF through blocking activation of JNK pathway.

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张晓明,罗玲,杨林,张丽娟,李倩,孙影,王瑞敏,魏中秋,杨方. N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸对大鼠心脏成纤维细胞c-Jun氨基末端激酶通路活化的影响[J].中国动脉硬化杂志,2010,18(6):437~440.

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  • 收稿日期:2010-01-19
  • 最后修改日期:2010-05-25
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