摘要
目的:探讨抗纤维化短肽N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(Ac-SDKP)经由Ang Ⅱ介导的细胞外信号调节激酶1/2(ERK1/2)的调节通路在大鼠血管纤维化形成中的作用。方法:采用差速贴壁法获取新生大鼠血管外膜成纤维细胞,随机分为对照组,Ang Ⅱ(10-6mmol/L)组,Ang Ⅱ+Ac-SDKP(10-9mmol/L)组和PD98059(细胞外信号调节激酶通路特异性抑制剂)(25μmmol/L)组,分别采用逆转录-聚合酶链反应(RT-PCR)检测I、ⅡI型胶原蛋白mRNA表达,Western blot印迹法检测MMP(基质金属蛋白酶)-2、TGF(转化生长因子)-β1蛋白的表达。结果:Ac-SDKP能显著抑制Ang Ⅱ刺激的胶原蛋白合成和TGF-β1蛋白表达,并上调MMP-2表达。ERK1/2通道特定阻断剂(PD98059)则明显减弱Ac-SDKP的上述作用。结论:Ac-SDKP可能是通过ERK1/2信号转导通道抑制Ang Ⅱ刺激的胶原蛋白合成,从而发挥有效的抗血管纤维化作用。
Objective： To investigate the effect of an anti-fibrotic tetra peptide Ac-SDKP on vascular fibrosis by regulating extracellular regulated protein kinase （ERK1/2） activity through Aug II. Methods： Rat vascular advenfitial fthroblasts were cultured /n vitro. They were randomly divided into control group, Ang II （10^-6mtrl/L） group, Ang II and Ac-SDKP joint action group, PD98059 group. Type I,m clagen contents in adventitia fibroblasts were measured by RT-PCR and the expressions of matrix metalloproteinases （MMP-2） and uamfonning growth factor-~ （ TGF-131 ） were determined by Western blot. Results： Ac-SDKP could reduced Ang II-induced expression of type I, m collagen secretion and TGF-at mRNA,and increase MMP-2 expression, PD98059 could inhibit the above effect. Conclusion： The results suggested that Ac-SDKP could inhibit the formation and development of vascular fibrosis through blocking ERK1/2 pathway mediated by Ang II. Ac-SD- KP therefore served as an antifibretic factor in vascular fibrosis.
出处
《中国应用生理学杂志》
CAS
CSCD
2013年第2期179-181,192,共4页
Chinese Journal of Applied Physiology
基金
皖南医学院弋矶山医院中青年研究项目(WK201040F)
