赖诺普利对自发性高血压大鼠血管平滑肌细胞离子泵活性及其mRNA表达的影响
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贵州省科学技术基金重点项目;;贵州省优秀青年科技人才基金项目[(2002)3013,(2003)0316]


Effects of Lisinopril on the Activities and mRNA Expression of Ion Pumps in Aortic Smooth Muscle Cells from Spontaneously Hypertensive Rats
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    目的探讨赖诺普利对自发性高血压大鼠动脉血管平滑肌细胞钠泵、钙泵活性及钠泵α1亚单位、钙泵亚型1mRNA表达水平的影响。方法以自发性高血压大鼠动脉血管平滑肌细胞为研究对象,分为自发性高血压大鼠对照组、低剂量(1×10-6mol/L)赖诺普利组和高剂量(1×10-5mol/L)赖诺普利组,另以Wistar-Kyoto大鼠(WKY)为对照;分别用生化酶学方法和实时定量PCR检测细胞膜钠泵、钙泵活性和mRNA表达水平,用放射免疫分析法检测细胞培养液血管紧张素Ⅱ的含量。结果与WKY对照组比较,自发性高血压大鼠动脉血管平滑肌细胞膜钠泵、钙泵活性及钠泵α1亚单位、钙泵亚型1mRNA表达水平均降低(P><0.01)。赖诺普利能提高自发性高血压大鼠动脉血管平滑肌细胞膜钠泵、钙泵活性,并能上调钠泵α1亚单位和钙泵亚型1mRNA的表达水平(P><0.01)。自发性高血压大鼠动脉血管平滑肌细胞培养液中血管紧张素Ⅱ含量高于WKY对照组(P><0.05),赖诺普利能降低其培养液中血管紧张素Ⅱ含量(P><0.05)。结论高血压大鼠动脉血管平滑肌细胞两种离子泵活性降低可能缘于它自身基因表达水平的下降,赖诺普利通过阻断血管紧张素Ⅱ而上调两种离子泵活性及基因表达。

    Abstract:

    Aim To explore the effects of lisinopril on the activities of Na+,K+-ATPase and Ca2++-ATPase and mRNA expression levels of Na+,K+-ATPase α1-subunit and plasma membrane Ca2++-ATPase isoform 1(PMCA1) in cultured thoracic aorta vascular smooth muscle cells (ASMC) isolated from spontaneously hypertensive rats (SHR). Methods ASMC were divided into four groups:Wistar-Kyoto (WKY) control,SHR control,Lisinopril(1×10-6)intervened SHR group and lisinopril(1×10-5)intervened SHR group. The activities of ion pumps were detected by spectrophotography and mRNA expression were measured by real time PCR. The content of angiotensin Ⅱ(AngⅡ) in cells-cultured medium were detected by radioimmunoassay. Results The activities of Na+,K+-ATPase,Ca2++-ATPase and the mRNA expression levels of Na+,K+-ATPase α1-subunit and PMCA1 in ASMC from SHR were significantly lower than those from WKY control (P><0.01). Lisinopril significantly increased the activities of Na+,K+-ATPase and Ca2++-ATPase and mRNA expression levels of Na+,K+-ATPase α1-subunit and PMCA1 in ASMC from SHR (P><0.01). AngⅡcontent of culture medium in ASMC from SHR was significantly more than those from WKY control(P><0.05),lisinopril attenuated AngⅡcontent of ASMC culture medium from SHR (P><0.05). Conclusion The decreased activities of Na+,K+-ATPase and Ca2++-ATPase may be related to their lower expression of the mRNA in ASMC from SHR. The lisinopril may increase the activities of two ion pumps and upregrulae the mRNA expression of Na+,K+-ATPase α1-subunit and PMCA1 in ASMC from SHR through blocking the generation of AngⅡ.

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郭玉璜,商黔惠,吴芹,姜黔峰,张贵海.赖诺普利对自发性高血压大鼠血管平滑肌细胞离子泵活性及其mRNA表达的影响[J].中国动脉硬化杂志,2010,18(6):441~444.

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  • 收稿日期:2010-04-19
  • 最后修改日期:2010-06-12
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