The Na+/Ca2+ exchanger plays an important role in regulation of airway smooth muscle contraction by regulating intracellular calcium, and is a potential target for treatment of asthma. To test modulation of exchanger ...The Na+/Ca2+ exchanger plays an important role in regulation of airway smooth muscle contraction by regulating intracellular calcium, and is a potential target for treatment of asthma. To test modulation of exchanger activity, we used Xenopus oocytes as model system. Na+/Ca2+ exchanger was expressed in the cells by microinjection of cRNA of the exchanger isoform NCX1. The activity of NCX1 was determined as Ni2+-sensitive current under voltage clamp in low Cl– medium and in the presence of the Cl–-channel inhibitor niflumic acid. Only this composition of solution allowed determining NCX1-mediated current with sufficient accuracy. Among a few tested Chinese herbal drugs, glycyrrhizic acid turned out to be a potent inhibitor of NCX1 with an apparent IC50 value of 40 μM. Previous work had revealed elevated cyclophylin A concentration in serum of asthmatic rats after receiving acupuncture treatment. Extracellular incubation of the oocytes in cyclophylin A for one day led to significant inhibition with an apparent IC50 value of about 1 μM. We suggest that effects of acupuncture and application of glycyrrhizic acid as an active constituent of Chinese medicine for treatment of asthma symptoms may partially be attributed to inhibition of the reversed mode of NCX1 and that these compounds may stimulate the search for new anti-asthmatic drugs.展开更多
目的探讨参松养心胶囊(SSYX)对心肌梗死后心律失常发生和心功能不全的影响及其作用机制。方法将40只新西兰大耳白兔行冠状动脉前降支结扎术后随机分为正常对照组(Control组)10只、心梗组(MI组)10只、心梗+胺碘酮组(MI+A组,0.4 g·kg...目的探讨参松养心胶囊(SSYX)对心肌梗死后心律失常发生和心功能不全的影响及其作用机制。方法将40只新西兰大耳白兔行冠状动脉前降支结扎术后随机分为正常对照组(Control组)10只、心梗组(MI组)10只、心梗+胺碘酮组(MI+A组,0.4 g·kg^(^(-1))·d^(^(-1)))10只、心梗+参松组(MI+S组,0.5 g·kg^(^(-1))·d^(^(-1)))10只。正常对照组开胸后在冠状动脉下穿线,但不结扎。术后,分别以普食、普食+胺碘酮粉末、普食+参松养心胶囊原粉喂食。8周后将家兔处死,在心梗周边区取材,检测各组白兔缝隙连接蛋白43(CX43)、钠钙交换体(NCX)和兰尼碱受体蛋白(Ry R2)m RNA的相对表达量。结果与Control组比较,MI组CX43、Ry R2 m RNA相对表达量显著下降(P<0.05),而NCX m RNA相对表达量虽然有所下降,但其差异无统计学意义(P>0.05);与MI组比较,MI+A组CX43、Ry R2 m RNA相对表达量显著升高(P<0.05),MI+S组CX43、NCX、Ry R2 m RNA的相对表达量也显著升高(P<0.05);与MI+A组比较,MI+S组CX43、NCX m RNA的相对表达量均显著升高(P<0.05)。结论参松养心胶囊可以改善心肌梗死后心律失常以及心功能不全,其机制可能与调控各钙离子通道的开放,抑制钙超载有关。展开更多
文摘The Na+/Ca2+ exchanger plays an important role in regulation of airway smooth muscle contraction by regulating intracellular calcium, and is a potential target for treatment of asthma. To test modulation of exchanger activity, we used Xenopus oocytes as model system. Na+/Ca2+ exchanger was expressed in the cells by microinjection of cRNA of the exchanger isoform NCX1. The activity of NCX1 was determined as Ni2+-sensitive current under voltage clamp in low Cl– medium and in the presence of the Cl–-channel inhibitor niflumic acid. Only this composition of solution allowed determining NCX1-mediated current with sufficient accuracy. Among a few tested Chinese herbal drugs, glycyrrhizic acid turned out to be a potent inhibitor of NCX1 with an apparent IC50 value of 40 μM. Previous work had revealed elevated cyclophylin A concentration in serum of asthmatic rats after receiving acupuncture treatment. Extracellular incubation of the oocytes in cyclophylin A for one day led to significant inhibition with an apparent IC50 value of about 1 μM. We suggest that effects of acupuncture and application of glycyrrhizic acid as an active constituent of Chinese medicine for treatment of asthma symptoms may partially be attributed to inhibition of the reversed mode of NCX1 and that these compounds may stimulate the search for new anti-asthmatic drugs.
文摘目的探讨参松养心胶囊(SSYX)对心肌梗死后心律失常发生和心功能不全的影响及其作用机制。方法将40只新西兰大耳白兔行冠状动脉前降支结扎术后随机分为正常对照组(Control组)10只、心梗组(MI组)10只、心梗+胺碘酮组(MI+A组,0.4 g·kg^(^(-1))·d^(^(-1)))10只、心梗+参松组(MI+S组,0.5 g·kg^(^(-1))·d^(^(-1)))10只。正常对照组开胸后在冠状动脉下穿线,但不结扎。术后,分别以普食、普食+胺碘酮粉末、普食+参松养心胶囊原粉喂食。8周后将家兔处死,在心梗周边区取材,检测各组白兔缝隙连接蛋白43(CX43)、钠钙交换体(NCX)和兰尼碱受体蛋白(Ry R2)m RNA的相对表达量。结果与Control组比较,MI组CX43、Ry R2 m RNA相对表达量显著下降(P<0.05),而NCX m RNA相对表达量虽然有所下降,但其差异无统计学意义(P>0.05);与MI组比较,MI+A组CX43、Ry R2 m RNA相对表达量显著升高(P<0.05),MI+S组CX43、NCX、Ry R2 m RNA的相对表达量也显著升高(P<0.05);与MI+A组比较,MI+S组CX43、NCX m RNA的相对表达量均显著升高(P<0.05)。结论参松养心胶囊可以改善心肌梗死后心律失常以及心功能不全,其机制可能与调控各钙离子通道的开放,抑制钙超载有关。
