ERK1/2及JNK通路在AcSDKP抑制PDGF诱导的大鼠心脏成纤维细胞增殖和胶原蛋白表达中的作用  

Effect of ERK1/2 and JNK in the inhibition of AcSDKP on the cell proliferation and collagen expression in rat cardiac fibroblasts induced by PDGF

作　　者：张丽娟[1] 张晓明 马文东[1] 李倩[1] 杨方[1] 王瑞敏[1] 

机构地区：[1]河北联合大学医学实验研究中心,河北省063000 [2]武警河北总队唐山市支队

出　　处：《江苏医药》2012年第7期752-755,共4页Jiangsu Medical Journal

基　　金：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)

摘　　要：目的探讨细胞外信号调节激酶1/2(ERK1/2)及C-Jun氨基末端激酶(JNK)通路在N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(AcSDKP)抑制血小板源性生长因子(PDGF)诱导的大鼠心脏成纤维细胞增殖和胶原蛋白表达中的作用。方法将新生Wistar大鼠心脏成纤维细胞分为对照组(A组)、10ng/ml PDGF刺激组(B组)、10-9 mol/L AcSDKP+10ng/ml PDGF干预组(C组)、25μmol/L PD98059+10ng/ml PDGF干预组(D组)和10nmol/L SP600125+10ng/ml PDGF干预组(E组)。MTT法检测心脏成纤维细胞代谢活性的变化,Western blot法检测大鼠心脏成纤维细胞中ERK1/2、JNK及磷酸化-ERK1/2、磷酸化-JNK蛋白表达和Ⅰ型、Ⅲ型胶原蛋白的表达。结果与A组相比,B组心脏成纤维细胞代谢活性、Ⅰ型及Ⅲ型胶原蛋白表达、磷酸化-ERK1/2及磷酸化-JNK蛋白表达均增强(P<0.05);而C、D、E组能明显逆转B组上述各观察指标的增加过程(P<0.05)。结论 AcSDKP能够通过阻断PDGF介导的ERK1/2及JNK通路的激活,进而抑制大鼠心脏成纤维细胞增殖和胶原蛋白表达。Objective To investigate the effect of extracellular signal regulated kinase1/2（ERK1/2） and C-Jun N-terminal kinase（JNK） pathways in the inhibition of N-acetyl-seryl-aspartyl-lysyl-proline（AcSDKP） on the cell proliferation and collagen expression in the rat cardiac fibroblasts induced by PDGF.Methods The neonatal Wistar rat cardiac fibroblasts were divided into five groups of A（normal controls）,B（stimulated with 10 ng/ml PDGF）,C（pretreated with 10-9 mol/L AcSDKP 30 min and then stimulated with 10 ng/ml PDGF）,D（pretreated with 25 mol/L PD98059 1 h and then stimulated with 10 ng/ml PDGF） and E（pretreated with 10 nmol/L SP600125 15 min and then stimulated with 10 ng/ml PDGF）.The metabolic activity of cardiac fibroblasts was observed by MTT assay.The protein expressions of ERK1/2,JNK,phospho-ERK1/2,phospho-JNK and typeⅠand type Ⅲ collagen in the cardiac fibroblasts were detected by Western blot.Results Compared with group A,the metabolic activity of cardiac fibroblasts and the protein expressions of phospho-ERK1/2,phospho-JNK and typeⅠand type Ⅲ collagen were increased in group B（P〈0.05）,which were all reversed in groups of C,D and E（P〈0.05）.Conclusion AcSDKP can inhibit the cell proliferation and collagen expression through blocking the ERK1/2 and JNK pathway activation induced by PDGF in the cardiac fibroblasts.

关 键 词：细胞外信号调节激酶1/2 C-Jun氨基末端激酶 N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸 血小板源性生长因子 

分 类 号：R542[医药卫生—心血管疾病]