己酮可可碱对高糖诱导肾小球系膜细胞结缔组织生长因子表达信号通路的影响

Impact of pentoxifylline on the pathway of high glucose-induced expression of connective tissue growth factor in mesangial cells

目的探讨高糖诱导大鼠肾小球系膜细胞结缔组织生长因子（CTGF）表达的变化及其作用通路，并且研究己酮可可碱（PTX）对CTGF表达的影响。方法体外培养大鼠系膜细胞，观察不同浓度的高糖在不同时间对系膜细胞转化生长因子β（TGF-β）、CTGF、p-Smad2／3、Smad7及纤连蛋白（FN）表达的影响；并在高糖培养液中加入TGF—B中和抗体及不同浓度的PTX观察其对上述各指标表达的影响。结果高糖可以诱导系膜细胞TGF-β、CTGFmRNA及蛋白表达增加（均P〈0．05），且呈时间、剂量依赖性，同时伴有p-Smad2／3蛋白表达的增加及Smad7蛋白表达的减少。阻断TGF—β可使高糖诱导的CTGFmRNA及蛋白表达分别下降86．4％及91．8％（均P〈0．05）。PTX可以抑制高糖诱导的系膜细胞CTGFmRNA及蛋白表达，随着PTX浓度的增加其抑制作用更为显著（P〈0．05），但对于TGF—β的表达没有影响。结论高糖可通过TGF-β—Smads通路使CTGFmRNA表达增加进而影响其蛋白表达。PTX可以有效的抑制CTGF的表达而对于TGF—β的表达没有直接的抑制作用。

Objective To investigate the effect of pentoxifyccine （PTX） on the pathway of high glucosd-induced expression of CTGF in mesangial cells. Methods Cultured rat mesangial celld were used to study the influence of different concentration of high glucose on the expression of TGF-β, CTGF, p-Smad2/3, Smad7 and FN in different exposure time. Furthermore the effect of high glucose plus TG-β neutral antibody and different concentration of PTX on the obove expression was evaluated as well. Results High glucose could increase TG-β, CTGF mRNA and protein expression in mesangial cells （P〈0.05） in time- and dose-dependent manner, and at the same time p-Smad2/3 expression increased and Smad7 expression decreased （P〈0.05）. The blockage of TGF-S could decrease high glucose-induced CTGF mRNA and protein expression by 86.4% and 91.8%. PTX could suppress high glucose-induced CTGF expression in mesangial cells. When the PTX dosage increased, the suppressive effect became more remarkable, but PTX had no influence on the TGF-β expression. Conclusions High glucose up-regulates CTGF mRNA and protein expression mainly through TGF-β-Smads pathway. PTX can suppress CTGF expression effectively, but has no direct inhibition of TGF-β expression.