尾加压素Ⅱ促进乳鼠心肌成纤维细胞分泌胶原及增殖的细胞内信号转导机制  

Effect of urotensin Ⅱ on the proliferation of cardiac myofibroblasts and its intracellular signaling mechanism in new-born SD rats

作　　者：宋庆刚[1] 吕建庄[1] 杨竞霄[1] 

机构地区：[1]第四军医大学西京医院心内科,陕西西安710032

出　　处：《西安交通大学学报（医学版）》2007年第2期156-160,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

摘　　要：目的探讨尾加压素Ⅱ(UⅡ)促进乳鼠心肌成纤维细胞(CFs)分泌胶原及增殖的细胞内信号转导机制。方法体外培养CFs,采用免疫组织化学染色法及羟脯氨酸测定法分别观察不同浓度UⅡ作用下,CFs中磷酸化ERK1/2细胞灰度和CFs培养上清中胶原含量的变化;蛋白激酶C(PKC)抑制剂chelerythrine chloride(Che)、ERK1/2抑制剂PD98059和钙调神经磷酸酶(CaN)抑制剂cyclosporin A(CsA)各自对UⅡ诱导的细胞增殖的影响。结果在1×10-10、1×10-9、1×10-8mol/L UⅡ作用下,CFs培养上清中胶原含量均较对照组明显增加,而CFs中磷酸化ERK1/2细胞灰度均较对照组有显著降低(P<0.01);在1×10-7mol/L UⅡ作用下,上述各参数与对照组比较无统计学意义(P>0.05)。1×10-6mol/L Che+1×10-8mol/L UⅡ组、1×10-5mol/L PD98059+1×10-8mol/L UⅡ组和5μg/mLCsA+1×10-8mol/L UⅡ组的胶原含量均高于对照组而低于1×10-8mol/L UⅡ组(P<0.05)。1×10-6mol/L Che+1×10-8mol/L UⅡ组、1×10-5mol/L PD98059+1×10-8mol/L UⅡ组和5μg/mL CsA+1×10-8mol/L UⅡ组的p-ERK1/2的灰度低于对照组(P<0.01);1×10-6mol/L Che+1×10-8mol/L UⅡ组和5μg/mL CsA+1×10-8mol/LUⅡ组的p-ERK1/2的灰度高于1×10-8mol/L UⅡ组(P<0.01),而1×10-5mol/L PD98059+1×10-8mol/L UⅡ组与之比较则无统计学意义(P>0.05)。结论UⅡ具有促进CFs分泌胶原及增殖的作用,其作用可能是通过PKC/MAPK/CaN途径实现的。Objective To explore the effect of urotensin Ⅱ （UⅡ） on the proliferation of cardiac fibroblasts （CFs） and its intracellular signaling mechanism in new-born SD rats. Methods Isolated and cultured CFs from new-born SD rats were used, and cell proliferation was observed by immunohistochemical staining and hydroxyproline assay. Results With the treatment of 10^-10 , and 10^-9 , and 10^-8mol/L UⅡ , the collagen content in CFs supernatant was significantly higher than that in control group, the grey scale of p-ERK1/2 was significantly lower than that of control （P〈0.01）, while the indices in 10^-7 mol/L UⅡ group were not significantly different from those of control （P〉0.05）. Compared with that in control group, the collagen content in 10^-6 mol/L Che＋ 10^-8mol/L UⅡ and 5 μg/mL CsA＋10^-8 mol/L UⅡ groups increased （P〈0.05）, while no difference was found between 10^-5mol/L PD9805＋10^-8 mol/L UⅡ and control groups（P〉0.05）. Compared with those in control group, the grey scales of p-ERK1/2 in 10^-6 mol/L Che＋10^-8mol/L UⅡ , and 10^-5mol/L PD9805＋10^-8mol/L UⅡ , 5 μg/mL CsA＋10^-8 mol/L UⅡ groups declined significantly （P〈0.01）. In contrast to those in 10^-8 mol/L UⅡ group, the grey scales in 10^-6mol/L Che＋10^-8mol/L UⅡ and 5μ/mL CsA＋10^-8 mol/L UⅡ groups increased significantly（P〈0.01）, but had no difference for 10^-5 mol/L PD98059 ＋ 10^-8 mol/L UⅡ group （P 〉 0.05）. Conclusion UⅡ can stimulate the proliferation of CFs in new-born SD rats and the UⅡ -induced proliferation of CFs is probably mediated by PKC/MAPK/CaN.

关 键 词：尾加压素Ⅱ 心肌 成纤维细胞 细胞分裂 

分 类 号：R331[医药卫生—人体生理学]