氨酚伪麻美芬片Ⅱ对小鼠气管平滑肌的舒张作用

Relaxant effect of paracetamol,pseudoephedrine hydrochloride and dextromethorphan hydrobromide tabletⅡon tracheal smooth muscles in mice

目的探讨氨酚伪麻美芬片Ⅱ对小鼠气管平滑肌的舒张作用及其可能机制。方法将BALB/c小鼠处死后取下气管组织,放置在灌流槽内,用高钙离子溶液进行平衡。用激动剂乙酰胆碱(ACh)使气管进行收缩,等待肌张力曲线显示数值达到稳定期,观察气管环在不同浓度氨酚伪麻美芬片Ⅱ作用下张力的变化。将ACh预收缩处理的小鼠气管平滑肌中加入不同类型的离子通道阻断剂后,检测氨酚伪麻美芬片Ⅱ对小鼠气管平滑肌的作用。采用膜片钳技术和钙离子成像实验分别检测氨酚伪麻美芬片Ⅱ对L型钙离子通道和平滑肌细胞内钙离子浓度的影响。结果氨酚伪麻美芬片Ⅱ剂量依赖性地抑制了ACh引起的预收缩(P<0.05)。氨酚伪麻美芬片Ⅱ舒张高钾离子溶液诱导后的气管平滑肌收缩(P<0.05)。硝苯地平和Pyr3降低了ACh引起的气管平滑肌收缩(P<0.05);然后再加入氨酚伪麻美芬片Ⅱ,进一步抑制气管平滑肌的收缩(P<0.05)。氨酚伪麻美芬片Ⅱ可以抑制电压依赖性钙通道电流(P<0.05),并降低ACh诱导的气管平滑肌细胞内钙离子浓度(P<0.05)。结论氨酚伪麻美芬片Ⅱ对于气管平滑肌具有较强的舒张作用,其主要是通过L型钙离子通道和钙敏感通路来发挥作用。

Objective To investigate the relaxant effect and underlying mechanism of paracetamol>pseudoephedrine hydrochloride and dextromethorphan hydrobromide tabletⅡ(PPD-Ⅱ)on tracheal smooth muscles in mice.Methods The BALB/c mice were sacrificed for isolating the tracheal tissues,which were balanced with high Ca^(2+)solution in the perfusion bath.The trachea was contracted with the treatment of agonist acetylcholine(ACh).When the curve of muscular tension reached the stable phase,the changes of tracheal tension were recorded after treated with different concentrations of PPD-Ⅱ.The different kinds of ionic channel inhibitors were added into ACh-precontracted tracheal smooth muscles,and then the effect of PPD-Ⅱ on the tracheal smooth muscles was measured.The effect of PPD-Ⅱ on the L-type Ca^(2+)channel and concentration of intracellular Ca^(2+)were detected by patch-clamping and Ca^(2+)imaging techniques,respectively.Results The PPD-Ⅱinhibited the ACh-induced precontract in a dose-dependent manner(P<0.05)and relaxed high K^(+)solution-contracted tracheal smooth muscles(P<0.05).The nifedipine and Pyr3 decreased ACh-contracted tracheal smooth muscles(P<0.05),which was further inhibited by the treatment of PPD-Ⅱ(P<0.05).Moreover,PPD-Ⅱ inhibited the voltage-dependent calcium channel current and decreased the concentration of Ca^(2+)in tracheal smooth muscle cells induced by ACh(P<0.05).Conclusion The PPD-Ⅱ has obviously relaxant effect on the tracheal smooth muscles,which may be related with L-type Ca^(2+)channel and calcium-sensitive pathway.