Na^(+)/Ca^(2+)交换体抑制剂SN-6和维拉帕米降低肾上腺皮质癌细胞系NCI-H295R醛固酮合成酶表达  

Na^(+)/Ca^(2+)exchanger inhibitor SN-6 and verapamil reduce aldosterone synthase expression in adrenocortical carcinoma cell line NCI-H295R

作　　者：王宇[1,2] 高寅洁[2] 任卫东 童安莉[2] WANG Yu;GAO Yinjie;REN Weidong;TONG Anli(Graduate School,Hebei North University,Zhangjiakou 075000;Department of Endocrinology,Key Laboratory of Endocrinology of National Health Commission,Peking Union Medical College Hospital,CAMS&PUMC,Beijing 100730;Department of Endocrinology,the First Hospital Affiliated to Hebei North University,Zhangjiakou 075000,China)

机构地区：[1]河北北方学院研究生院,河北张家口075000 [2]中国医学科学院北京协和医学院、北京协和医院内分泌科、国家卫生健康委员会内分泌重点实验室,北京100730 [3]河北北方学院附属第一医院内分泌科,河北张家口075000

出　　处：《基础医学与临床》2024年第5期626-629,共4页Basic and Clinical Medicine

基　　金：国家重点研发计划(2021YFC2501600,2021YFC2501603);国家自然科学基金(82070822);中央高水平医院临床科研业务费(2022-PUMCH-C-028)。

摘　　要：目的研究Na^(+)/Ca^(2+)交换体(NCX)抑制剂SN-6和钙通道阻滞剂(CCB)维拉帕米对钾离子(K^(+))刺激的肾上腺皮质癌细胞系NCI-H295R(H295R)醛固酮合成酶表达的影响。方法H295R细胞分为对照组、K^(+)(15 mmol/L)处理组、钙通道阻滞剂维拉帕米(verapamil)(10μmol/L)处理组、SN-6(10μmol/L)处理组、K^(+)+维拉帕米处理组、K^(+)+SN-6处理组、维拉帕米+SN-6处理组和K^(+)+维拉帕米+SN-6处理组,用实时荧光定量PCR检测醛固酮合成酶(CYP11B2)的mRNA表达,用FLIPR Calcium6检测细胞内钙离子水平。结果与对照组相比,K^(+)刺激醛固酮合成酶CYP11B2的mRNA表达(P<0.001);SN-6和维拉帕米均抑制K^(+)刺激的CYP11B2的mRNA表达(P<0.01);与K^(+)+SN-6组相比,K^(+)+SN-6+维拉帕米组更能显著抑制CYP11B2的mRNA表达(P<0.001)。SN-6和维拉帕米显著降低K^(+)刺激的细胞内钙离子水平(P<0.0001)。结论SN-6和维拉帕米均抑制K^(+)诱导的H295R细胞的醛固酮合成酶的表达;SN-6联合维拉帕米处理,抑制作用更显著。Objective To investigate the effect of Na^(+)/Ca^(2+)exchanger inhibitors SN-6 and calcium channel blocker verapamil on potassium-stimulated expression of aldosterone synthase in adrenocortical carcinoma cell line NCI-H295R(H295R).Methods H295R cells were treated in different groups,including control group,K^(+)(15 mmol/L)treated group,verapamil(10μmol/L)group,SN-6(10μmol/L)group,combination of K^(+)/verapamil treated group,combination of K^(+)/SN-6 treated group,combination of K^(+)/verapamil and SN-6 treated group.Real-time PCR was used to detect the mRNA expression of aldosterone synthetase(CYP11B2),and FLIPR Calcium 6 was used to detect the intracellular calcium ion level.Results Compared with the control group,K^(+)stimulated CYP11B2 mRNA expression.Both SN-6 and verapamil decreased K^(+)induced CYP11B2 mRNA expression(P<0.01).Compared with the K^(+)+SN-6 treated group,the K^(+),SN-6 and verapamil treated group all significantly inhibited CYP11B2 mRNA expression(P<0.001).Both of SN-6 and verapamil significantly reduced the intracellular calcium level stimulated by K^(+)(P<0.0001).Conclusions Both SN-6 and verapamil inhibit K^(+)-induced expression of aldosterone synthase in adrenocortical carcinoma H295R cells.The inhibitory effect is more significant when treated by the combination of verapamil and SN6.

关 键 词：SN-6 维拉帕米 NCI-H295R细胞 细胞内钙离子 CYP11B2 

分 类 号：R586.9[医药卫生—内分泌]