15-脱氧-△^(12,14)-前列腺素J2在兔肾近曲小管钠和碳酸氢根转运作用及机制

Effects and Mechanisms of 15-deoxy-△^(12,14)-prostaglandin J2 on Na+/HCO3-Transport in Rabbit Renal Proximal Tubular

目的探讨过氧化物酶体增生物活化受体-γ(PPAR-γ)的选择性配体15-脱氧-△12,14-前列腺素J2(15d-PGJ2)在兔肾近曲小管钠和碳酸氢根的转运作用及其传导通路。方法在15d-PGJ2(0.1、0.3、1.0、10.0μmol/L)及PPAR-γ拮抗剂(5μmol/LGW9662)或MAPKK/MEK抑制剂(10μmol/LPD98059)作用下,观察兔肾近曲小管钠和碳酸氢根转运活动度的变化,Western blotting法测定细胞外信号调节激酶(extracellular signal regulated kinase,ERK)的磷酸化。结果 15d-PGJ2刺激兔肾近曲小管钠和碳酸氢根的转运,随浓度增加刺激作用增强。0.3μmol/L15d-PGJ2引起的刺激作用被MAPKK/MEK抑制剂及PPAR-γ拮抗剂阻止。PPAR-γ的两种选择性配体0.3μmol/L15d-PGJ2和0.3μmol/L吡格列酮刺激ERK磷酸化,并被PPAR-γ拮抗剂阻滞。结论通过PPAR-γ依赖的ERK磷酸化介导15d-PGJ2在兔肾近曲小管钠和碳酸氢根的转运。

Objective To examine the effects of 15-deoxy-△12,14-prostaglandin J2 （15d-PGJ2）, the selective ligand of PPAR-7, on Na＋/HCO3- transport in rabbit proximal tubular and the underlying mechanisms. Methods The responses Na＋/HCO3- eotransporter induced by different 15d-PGJ2 concentrations were compared in isolated rabbit renal proximal tubules, with or without MAPKK/MEK inhibitor PD98059 or PPAR-У antagonist GW9662. The phospholipase of ERK was examined by Western blotting. Results 15d-PGJ2 stimulated the activity of Na＋/HCO3- cotransporter with the concentration increase （0.1 umol/L, 0.3 umol/L, 1 umol/L and 10 umol/L）. The stimulation of NBC activity induced by 0.3 umol/1 of 15d-PGJ2 was inhibited by a MAPKK/MEK inhibitor PD98059 as well as by a PPAR- У antagonist GW9662. In rabbit renal tubular, 0.3 umol/L dPGJ2 and 0.3 umol/L pioglitazone both induced the ERK phosphorylation but it was inhibited by PPAR-У antagonist. Conclusion The PPAR-T-dependent ERK activation was involved in PPAR-У ligand （15-dPGJ2）-induced Na＋/HCO3- cotransport stimulation in rabbit renal proximal tubular.