高碘促成纤维细胞增殖作用与成纤维细胞生长因子及其受体的关系

Research on the relationship between bFGF, FGFR2 and the fibroblast proliferation promoted by high density iodine

目的研究高碘促进成纤维细胞增殖作用与碱性成纤维细胞生长因子(bFGF)、成纤维细胞生长因子2型受体(FGFR2)的关系,探索高碘因素在布-加综合征(BCS)隔膜组织形成过程中的作用机制。方法①将体外培养的成纤维细胞分成对照组、溶媒组、KI组、FGFR抑制剂组和KI与FGFR抑制剂共同作用组,采用CCK-8法检测各组成纤维细胞增殖率。②采用免疫印迹法检测不同碘浓度(0、250、500、1 000、2 000、3 000μg/L)培养环境中bFGF、FGFR2蛋白表达量。多组间比较采用单因素方差分析(ANOVA),多个实验组与1个对照组比较采用最小显著差法(LSD)。结果①在1 000μg/L碘浓度组,KI与FGFR抑制剂共同作用组成纤维细胞增殖率(1.06±0.13)高于FGFR抑制剂组(0.40±0.12),而低于KI组(1.73±0.09),组间差异有统计学意义(P<0.05)。②在500、1 000μg/L碘浓度组,FGFR2蛋白相对表达量高于其他碘浓度组,而1 000μg/L组高于500μg/L组,组间差异有统计学意义(P<0.05)。各碘浓度组间bFGF蛋白相对表达量差异无统计学意义(P>0.05)。结论①高碘因素可能通过上调FGFR2蛋白表达量而引起成纤维细胞增殖;②高碘导致的成纤维细胞增殖可能与隔膜形成相关。

Objective To investigate the relationship between fibroblast proliferation promoted by high density iodine and basic fibroblast growth factor （bFGF） as well as fibroblast growth factor receptor type 2 （FGFR2）,and to explore the mechanism of high density iodine in causing the formation of membrane in Budd-Chiari syndrome （BCS）.Methods ① The fibroblasts,which were cultured in high density of iodine in vitro,were divided into 5 groups：control group,solvent group,KI group,FGFR inhibitor group and combination group （FGFR inhibitor together with Kl）.The proliferation rate of fibroblasts of each group was determined by CCK-8 assay.② The FGFR2 protein expression level of bFGF and FGFR cultured in different concentrations of iodine （0,250,500,1 000,2 000 and 3 000 ug/L） was determined by Western-blot method.Quantitative data difference between groups was analyzed by one-way ANOVA method.LSD method was used to compare the experimental group with control group.Statistical significant was given in P values,the difference was considered to be statistically significant when P 〈 0.05.Results ① In iodine density of 1 000 ug/L,the proliferation rate of fibroblasts in combination group was （1.06 ± 0.13）,which was higher than that in FGFR inhibitor group （0.40 ± 0.12） and lower than that in KI group （1.73 ± 0.09）,the difference was statistically significan （P 〈 0.05）.② The FGFR2 protein expression level of fibroblasts in iodine density of 500 ug/L and 1 000 ug/L was higher than those in other iodine densities.The FGFR2 protein expression level in 1 000 ug/L group was higher than that in 500 ug/L group （P 〈 0.05）.The difference in bFGF protein expression level between each other group was not significant （P 〉 0.05）.Conclusion ① High density of iodine may promote the proliferation of fibroblasts by adjusting the protein expression level of FGFR2 upward.② The proliferation of fibroblasts caused by high iodine density may result in the formation of membrane in Budd-Chiari syndrome.