醛固酮對乳鼠期大鼠心肌細胞表達Cx43之影響

背景：腎素-血管緊張素-醛固酮系統(tǒng)可通過多種病理條件來影響心臟細胞形態(tài)和功能。本研究揭示醛固酮對心肌細胞表達縫隙連接蛋白Cx43的影響。
方法與結果：培養(yǎng)好的乳鼠期大鼠心肌細胞暴露于醛固酮24小時，檢測Cx43蛋白和mRNA表達量。通過多電極陣列系統(tǒng)（Med-64）檢測刺激全過程。用10-8mol/L的醛固酮處理心肌細胞，其Cx43 增加1.5倍，mRNA增加1.2倍 。Cx43免疫反應信號也有所增加。傳導速度(CV) 增加了 24 % 。用較高濃度（ 10-6 -10-4mol/L）醛固酮處理肌細胞，其Cx43蛋白減少0.3倍 ，但Cx43 mRNA水平保持不變， CV降低了23 % 。經(jīng)依普利酮預處理的肌細胞，再經(jīng)10-8mol/L的醛固酮處理，Cx43不增加，CV也不增加，但米非司酮對其不產生此影響。經(jīng)依普利酮或米非司酮預處理的心肌細胞，再經(jīng)10-6 到10-4mol/L醛固酮處理，其Cx43表達量減少。
結論：醛固酮可能是通過對表達Cx43的雙重影響來參與心律失常間隙連接重構的。

Effects of aldosterone on cx43 gap junction expression in neonatal rat cultured cardiomyocytes.

Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine.

Background: The renin-angiotensin-aldosterone system affects cellular morphology and function in the heart under a variety of pathologic conditions. In the present study the effects of aldosterone on the expression of connexin (Cx) 43 gap junctions in cardiomyocytes were investigated. Methods and Results: Cultured rat ventricular myocytes were exposed to aldosterone for 24 h. The protein and mRNA expression of Cx43 was estimated. Propagation of excitation was visualized by a multiple electrode array system. Treatment of the myocytes with 10(-8) mol/L aldosterone resulted in a significant upregulation of Cx43 (by ~1.5-fold in protein and by ~1.2-fold in mRNA). The immunoreactive signal of Cx43 was also increased. Conduction velocity (CV) was increased by ~24%. Treatment of the myocytes with aldosterone at higher concentrations (10(-6)-10(-4) mol/L) caused a significant downregulation of Cx43 protein (by ~0.3-fold) without affecting Cx43 mRNA levels, and decreased the CV by ~23%. The Cx43 upregulation and CV acceleration at 10(-8) mol/L aldosterone were prevented by pretreatment with eplerenone, but unaffected by mifepristone. Pretreatment of the myocytes with eplerenone or mifepristone did not prevent the Cx43 downregulation by aldosterone at 10(-6)-10(-4) mol/L. Conclusions: Aldosterone may be involved in arrhythmogenic gap junction remodeling through its dual effects on the expression of Cx43. (Circ J 2009; 73: 1504 - 1512).

文章來源：
http://www.ncbi.nlm.nih.gov/pubmed/19531903?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_
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