巴豆醛抑制小鼠心肌收缩功能

Crotonaldehyde inhibits myocardial contractile function in mice

目的研究香烟烟雾中α,β-不饱和醛-巴豆醛对小鼠心肌细胞收缩功能和心肌细胞内Ca^(2+)功能的影响。方法经Langendorff装置灌注消化分离出C57BL/6小鼠心肌细胞,与不同浓度(1、10、25和50μmol/L)巴豆醛孵育6 h,对照组不经巴豆醛处理,然后分别检测心肌细胞收缩峰值(PS)、最大收缩和舒张速率(±dL/dt)、心肌细胞收缩峰值时间(TPS)、心肌细胞舒张90%时间(TR_(90))、fura-2荧光强度(FFI)、细胞内Ca^(2+)衰退和SERCA^(45)Ca^(2+)摄取,Western blot分析Na^+-Ca^(2+)交换体的表达。结果与对照组相比,较高浓度(25和50μmol/L)的巴豆醛组能明显降低心肌细胞PS、±dL/dt、ΔFFI、SERCA活性及Ca^(2+)衰退速度(P<0.05),并能延长TR_(90)(P<0.05);而不同浓度巴豆醛对小鼠心肌细胞Na^+-Ca^(2+)交换体的表达无明显影响。结论巴豆醛可能是通过抑制小鼠心肌细胞内SERCA活性来影响心肌细胞内Ca^(2+)功能,从而抑制心肌细胞的收缩功能。

Objective To study the effect of an essentialα,β-unsaturated aldehyde from cigarette smoke crotonaldehyde on myocardial contractile function and intracellular Ca 2+function in mice.Methods Hearts of from male C57BL/6 mice were digested by Langendorff to islate the cardiomyocytes.The cardiomyocytes of mice were then incubated with crotonaldehyde(1,10,25 and 50μmol/L)for 6 h,and the control group was treated without crotonaldehyde,then they were evaluated including peak shortening(PS),maximal velocity of shortening/relengthening(±dL/dt),time-to-PS(TPS),time-to-90%relengthening(TR 90),fura-2 fluorescence intensity(FFI),intracellular Ca 2+decay and SERCA 45 Ca 2+uptake and the expression of Na+-Ca 2+exchange were evaluated by Western blot analysis.Results Compared with the control group,the higher concentrations of the crotonaldehyde(25 and 50μmol/L)groups significantly diminished the PS,±dL/dt,ΔFFI,SERCA activity and Ca 2+decay(P<0.05),as well as prolonged the TR 90(P<0.05);however the crotonaldehyde with different concentrations had no effect on the expression of Na+-Ca 2+exchange in cardiomyocytes.Conclusions Crotonaldehyde may inhibit cardiomyocyte contraction by suppressing SERCA activity and compromising intracellular Ca 2+handling.