目的研究藏药三味檀香散对离体大鼠肺小动脉的舒张作用并探讨其可能机制。方法利用去甲肾上腺素(NE)和氯化钾(KCl)预收缩离体大鼠肺小动脉,比较三味檀香散95%乙醇提取物和水提物的舒血管作用;研究不同工具药对醇提物舒血管作用的影响。结果三味檀香散醇提物和水提物均可抑制NE(1μmol·L-1)引起的肺小动脉的收缩作用。其中,醇提物的舒血管作用更优,两者比较,差异具有统计学意义(P〈0.05)。在浓度为0.3、0.9mg/mL时,水提物对KCl(60mmol·L-1)预收缩血管环的作用优于醇提物(P〈0.05)。在0.6、0.9mg/mL时,一氧化氮舍酶阻断剂左旋硝基精氨酸甲酯(L—NAME,100μmol·L-1)和前列环素合酶阻断剂吲哚美辛(IMT,10μmol·L-1)均能抑制醇提物对肺小动脉环的舒张作用(P〈0.05),在0.9mg/mL浓度时,IMT的阻断作用优于L-NAME。电压依赖性K+通道(Kv)阻断剂4-氨基吡啶(4-AP,1mmol·L-1)、内向整流K+通道(KIR)阻断剂氯化钡(BaCl2,1mmol·L-1)、钙激活K+通道(Kca)阻断剂四乙基氯化铵(TEA)均可抑制醇提物对肺小动脉环的舒张作用(P〈0.05)。结论三味檀香散95%醇提物对NE预收缩血管环的舒张作用优于水提物。药物醇提物舒张大鼠肺小动脉的可能作用机制:1)通过抑制细胞膜受体门控性钙通道,减少Ca2+流入血管平滑肌细胞引起血管舒张;2)作用于肺小动脉内皮,促进内皮细胞释放一氧化氮(NO)和前列环素(PGI2)至平滑肌使平滑肌舒张;3)作用于肺小动脉平滑肌的钾离子通道(Kv,K1R,KCa),促进通道开放引起血管平滑肌舒张。
Objective To investigate the Tibetan medicinal complex Sanweitanxiang powder(SWTXP) on rat pulmonary artery vasorelaxatioan in vitro and it's mechanism.Methods NE and KCl pre-contracted pulmonary artery vascular tings method in vitro was used to detect the effects of aqueous extract and 95% ethanol extract of SWTXP.The effects of different tool drugs on rat's pulmonary artery vasorelaxation by 95% ethanol extract were studied.Results The effect of pulmonary artery contraction with NE was inhibited by the aqueous extract and 95% ethanol extract.The effect of 95% ethanol extract on NE pre-contracted pulmonary artery vascular tings was better than that of the aqueous extractand showed significant statistical difference(P〈0.05).The effect of aqueous extract on KC1 pre-contracted pulmonary artery vascular tings was better than that of the 95% ethanol extract at concentration of 0.3mg/mL and 0.9mg/mL(P〈0.05) .And the effect of pulmonary artery vasorelaxation of the 95% ethanol extract was inhibited by adding L-NAME( 100μmol·L-1) and IMT( 10μmol·L-1) at 0.6mg/mL.And IMT performed a better inhibition effect than that of L-NAME at 0.9mg/mL (95% ethanol extract).Additionally, the pulmonary artery vasorelaxation of the 95% ethanol extract was also inhibited by 4-AP( 1mmol·L-1) ,BaC12( 1mmol·L-1 ) and TEA( 1mmol·L-1 ).Con- elusions The effect of 95% ethanol extract on NE pre-contracted pulmonary artery vascular tings was better than that of the deionized water extract.And the mechanism weve included as follows: 1 )The vasorelaxation effect was based on inhibiting receptor-operated calcium channel which reducing intracellular Ca2+ levels;2)The 95% ethanol extract could increase NO and PGI2 concentration by influencing pulmonary artery endothelium which played a role in inducing pulmonary artery vasorelaxation ;3)The 95% ethanol extract could induce vasorelaxation by opening the potassium ion channels( Kv,K1R and KCa)