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[氨氯吡咪通过抑制钠氢交换体-1减轻缺氧诱导的大鼠肺动脉平滑肌细胞增殖]

[Amiloride attenuates hypoxia-induced proliferation of rats pulmonary artery smooth muscle cells by suppressing Na+/ H+ exchanger-1].

作者信息

Liu Yi, Dong Ming-qing, Niu Wen, Zhang Bo, Luo Ying, Li Zhi-chao

机构信息

Department of Pathophysiologvy, Fourth Military Medical University, Xi'an 710032, China.

出版信息

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2007 Nov;23(4):462-5.

Abstract

AIM

To study the influence of Na+/H+ exchange inhibitor amiloride on hypoxia-induced proliferation in rats pulmonary artery smooth muscle cells (PASMCs), also observe the change of Na+/H+ exchanger-1 (NHE-1) activity and expression.

METHODS

Rats PASMGs were cultured in normoxia (21% O2) or hypoxia (2%O2) for 24 hours, as well as administered amiloride with various concentrations, cultured for 24 hours, then determined MTT OD values and rates of PCNA positive cells to investigate cells proliferation, moreover intracellular pH was determined by interactive Laser Cytometer, and Na+/H+ exchanger-1 mRNA expression was determined by RT-PCR.

RESULTS

Hypoxic exposure heightened intracellular pH and mRNA expression of NHE-1 in PASMCs, however, 3.123-50 micromol/L amiloride depressed them gradually. Additionally, hypoxic exposure raised MTT OD value and rates of PCNA positive cells, similarly, the above two indexes descended gradually with presence of 3.125-50 micromol/L amiloride.

CONCLUSION

Na+/H+ exchange inhibitor amiloride can suppress hypoxia-induced proliferation in pulmonary artery smooth muscle cells, which is due to depress activity and expression of NHE-1.

摘要

目的

研究钠/氢交换抑制剂氨氯地平对大鼠肺动脉平滑肌细胞(PASMCs)缺氧诱导增殖的影响,并观察钠/氢交换体-1(NHE-1)活性及表达的变化。

方法

将大鼠PASMGs在常氧(21% O2)或缺氧(2% O2)条件下培养24小时,以及给予不同浓度的氨氯地平并培养24小时,然后测定MTT OD值和PCNA阳性细胞率以研究细胞增殖,此外通过交互式激光细胞仪测定细胞内pH值,并通过RT-PCR测定钠/氢交换体-1 mRNA表达。

结果

缺氧暴露使PASMCs细胞内pH值和NHE-1 mRNA表达升高,然而,3.123 - 50 μmol/L氨氯地平使其逐渐降低。此外,缺氧暴露使MTT OD值和PCNA阳性细胞率升高,同样,随着3.125 - 50 μmol/L氨氯地平的存在,上述两个指标逐渐下降。

结论

钠/氢交换抑制剂氨氯地平可抑制缺氧诱导的肺动脉平滑肌细胞增殖,这是由于其降低了NHE-1的活性和表达。

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