长期睾酮缺失对雄性大鼠胸主动脉平滑肌细胞电压依从性钾通道的影响

Effect of long-term endogenous testosterone deprivation on function of voltage-dependent potassium channels in rat aortic artery

目的:研究去势后长期睾酮缺失对雄性大鼠主动脉平滑肌细胞电压依从性钾通道(Kv)的影响。方法:雄性Wistar大鼠去势后6个月,用张力换能器测量主动脉环等长张力,全细胞膜片钳和Western blotting技术检测电压依从性钾通道的功能和Kv1.5通道蛋白的变化。结果:雄性大鼠去势后6个月,电压依从性钾通道阻断剂(4-氨基吡啶,4-AP)对主动脉环的收缩明显降低。去势组主动脉平滑肌细胞电压依从性钾通道的幅度与对照组相比明显降低,同时Kv1.5通道蛋白表达也相应降低,应用生理剂量睾酮替代治疗后电压依从性钾通道的功能和转录后改变都有所恢复。结论:长期内源性睾酮缺失引起电压依从性钾通道功能衰减,Kv1.5通道蛋白表达可解释该改变,生理剂量的睾酮替代治疗对受损的电压依从性钾通道有修复作用。

AIM： To explore the effect of long- term （6 months） endogenous testosterone deprivation by orchidectomy on the function of voltage - dependent potassium channels of vascular smooth muscle cells in rats. METHODS： Wistar rats were raised for 6 months after castration. Isometric tension measurement of aortic rings, whole - cell patch -clamp technique and Western blotting analysis were employed to examine the functional and posttranscriptional alterations of voltage - dependent potassium channels. RESULTS： Voltage - dependent potassium channel blocker, 4 - aminopyridine, significantly decreased the constriction of aortic artery rings from male rats after 6 - month castration. In castrated rats the amplitude of voltage - dependent potassium currents of aortic artery smooth muscle cells was significantly decreased compared with that in control rats. Meanwhile, the expression of Kv 1.5 channel protein, which plays an essential role in mediating vasomotor function, was also reduced. The functional and molecular alterations of voltage - dependent potassium channels were both restored when the rats were concomitant applied with physiological level of testosterone after castration. CONCLUSION ： Long - term deprivation of endogenous testosterone in rats significantly attenuates the function of voltage - dependent potassium channels, and the decreases in expression of Kvl. 5 channel protein accounts for this alteration. Long - term application of physiological concentration of testosterone, which recovered the impaired function of voltage - dependent channels, may be beneficial for male gender with hypotestosteronaemia.