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目的研究吡格列酮对钠氢离子转运体(NHE1)的转运作用及传导通路,探讨噻唑烷二酮类药物引起水肿的机制。方法野生及PPARγ~(-/-)鼠胚胎成纤维细胞分为:对照组(DMEM培养液),ERK抑制剂(10μmol/L PD98059)组,PPARγ拮抗剂(5μmol/L GW9662)组,基因转录抑制剂(5μmol/LActiomycin D)组。测定各组细胞在0.3μmol/L吡格列酮灌注下NHE1的活性,Western blot法测定ERK磷酸化。结果吡格列酮增加野生鼠NHE1活性48.1%±3.1%,其作用被ERK抑制剂及PPARγ拮抗剂阻止,而不被基因转录抑制剂阻止;吡格列酮刺激野生鼠ERK磷酸化,对PPARγ~(-/-)鼠无此作用。结论吡格列酮经PPARγ/ERK通路,不依赖基因转录,刺激鼠胚胎成纤维细胞NHE1的转运,促进钠潴留。
Objective To study the translocation and transduction pathways of pioglitazone to sodium hydrogen ion transporter (NHE1) and to explore the mechanism of thiazolidinedione drug induced edema. Methods Fibroblasts from wild and PPARγ ~ (- / -) mice were divided into control group (DMEM), ERK inhibitor (10μmol / L PD98059) and PPARγ antagonist (5μmol / L GW9662) Inhibitor (5 μmol / LActiomycin D) group. The activity of NHE1 in each group was determined by perfusing pioglitazone 0.3μmol / L. The phosphorylation of ERK was determined by Western blot. Results Pioglitazone increased the activity of NHE1 in wild mice by 48.1% ± 3.1%, and its effect was blocked by ERK inhibitors and PPARγ antagonists, but not by gene transcription inhibitors. Pioglitazone stimulated the phosphorylation of ERK in wild mice, Rats do not have this effect. Conclusion Pioglitazone stimulates the transport of NHE1 in murine embryonic fibroblasts and promotes sodium retention via PPARγ / ERK pathway, independent of gene transcription.