【摘要】 目的 探讨原发性醛固酮增多症患者血液和组织中二十二碳六烯酸(docosahexaenoic acid, DHA)对肾上腺皮质细胞中醛固酮合成的作用及其潜在的作用靶点。方法 单侧和双侧原发性醛固酮患者60例。利用质谱法检测患者外周血及单侧原发性醛固酮增多症术后病理组织中DHA浓度。采用HAC15肾上腺皮质细胞作为体外模型，比较不同浓度(0、20、80、200μM)的DHA对其细胞增殖活力CCK-8的影响。分析DHA干预后HAC15醛固酮分泌量，醛固酮合成限速酶CYP11B2的蛋白和mRNA表达变化。使用钙离子荧光检测分析DHA对钙信号的影响。结果 单侧原发性醛固酮增多症患者外周血DHA水平高于双侧原发性醛固酮增多症，醛固酮腺瘤患者组织病理显示瘤体DHA水平高于周边皮质。DHA药物对HAC15细胞的增殖有抑制作用，细胞增殖率显著下降(P<0.05),但并未显著诱导细胞凋亡。DHA干预后，HAC15细胞醛固酮分泌明显增高(P<0.001),CYP11B2的蛋白和mRNA均上调，细胞内钙离子水平也显著升高(P<0.001)。结论 DHA可能通过调控钙信号途径促进CYP11B2的表达促进HAC15醛固酮的合成与分泌。更多还原

【Abstract】 Objective To investigate the effect of docosahexaenoic acid(DHA) in the blood and tissues of patients with primary aldosteronism(PA) on aldosterone synthesis in adrenocortical cells and its potential targets of action.Methods Sixty patients with unilateral and bilateral PA were selected. The concentration of DHA in peripheral blood of the patients and in pathologic tissues after surgery for unilateral PA was measured using mass spectrometry. HAC15 adrenocortical cells were used as an in vitro model. The effects of different concentrations of DHA(0, 20, 80, and 200 μM) on the cell proliferation activity of CCK-8 was compared. The aldosterone secretion, and the changes of protein and mRNA expression of CYP11B2 were analyzed. The effect of DHA on calcium signaling was analyzed using calcium ion fluorescence assay.Results Peripheral blood DHA levels were higher in patients with unilateral PA than those in patients with bilateral PA. Histopathology of patients with aldosterone adenoma(APA) showed higher tumor DHA levels than those of the peripheral cortex.The DHA drug had an inhibitory effect on the proliferation of HAC15 cells with a significant decrease in the rate of cell proliferation(P<0.05) but did not significantly induce apoptosis. Aldosterone secretion was significantly higher in HAC15 cells after DHA intervention(P<0.001). The protein and mRNA of CYP11B2 were up-regulated, and the intracellular calcium ion level was also significantly elevated(P<0.001).Conclusions DHA may promote the expression of CYP11B2 to indorse the synthesis and secretion of HAC15 aldosterone by regulating the calcium signaling pathway.更多还原