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目的研究AT2受体激动剂CGP42112对肾脏近曲小管上皮细胞(RPT)AT1受体表达的影响及其作用机制。方法以WKY(Wistar-Kyoto)大鼠的RPT细胞株为研究对象,采用免疫印迹法测定AT2受体激动剂CGP42112对AT1受体蛋白表达的影响,RT-PCR检测AT1受体mRNA表达水平的改变,硝酸还原酶法检测一氧化氮(nitric oxide,NO)含量。结果 AT2受体激动剂CGP42112 10-7mol/L作用24 h可以明显抑制WKY大鼠RPT细胞AT1受体的蛋白与mRNA表达水平(P<0.05)。CGP42112对AT1受体表达的抑制作用可被AT2受体特异性拮抗剂PD123319(10-6mol/L)所阻断。与对照组比较,CGP42112刺激RPT细胞30 min后,NO的合成含量明显升高;NO合成酶抑制剂L-NAME(10-4mol/L)可以阻断CGP42112对AT1受体表达的抑制效应。结论 AT2受体能够抑制WKY大鼠RPT细胞AT1受体的表达水平,该作用可能与NO途径有关。
Objective To investigate the effect of AT2 receptor agonist CGP42112 on the expression of AT1 receptor in renal proximal tubule epithelial cells (RPT) and its mechanism. Methods The effects of AT2 receptor agonist CGP42112 on AT1 receptor protein expression in Wistar-Kyoto rat RPT cell line were investigated by Western blotting. The expression of AT1 receptor mRNA was detected by RT-PCR , Nitrate reductase method to detect nitric oxide (NO) content. Results Apoptosis of AT1 receptor mRNA and protein in RPT cells of WKY rats was significantly inhibited by 10-7mol / L of AT2 agonist CGP42112 for 24 h (P <0.05). The inhibitory effect of CGP42112 on AT1 receptor expression can be blocked by the AT2 receptor specific antagonist PD123319 (10-6mol / L). Compared with the control group, the synthesis of NO was significantly increased after RPG cells were stimulated by CGP42112 for 30 min, while NO synthase inhibitor L-NAME (10-4 mol / L) blocked the inhibitory effect of CGP42112 on AT1 receptor expression. Conclusion AT2 receptor can inhibit the expression of AT1 receptor in RPT cells in WKY rats, which may be related to the NO pathway.