羟基红花黄色素A对猪冠状动脉的舒张作用及机理研究
摘要
目的：冠状动脉是心血管疾病研究的重要靶器官,冠状动脉粥样硬化可引发心肌缺血缺氧或坏死,是心血管疾病共同的病理基础,因此作用于冠状动脉的药物是心血管药物研发的一大重点。本实验研究了查耳酮类,传统活血化瘀药红花中含量最高的水溶性单体成分——羟基红花黄色素A对于离体猪冠状动脉血管的作用,并讨论了其可能的作用机制,为红花生物学活性的研究和应用提供参考。方法：以猪冠状动脉血管环为材料,离体血管功能实验方法检测羟基红花黄色素A的血管活性作用。
结果：羟基红花黄色素A对猪冠状动脉环的静息张力无明显作用,但对预收缩的血管具有浓度依赖性舒张作用,最大舒张效应为124.22±6.25%,相应的pD2值为2.91±0.23; HSYA可使KCl的量效曲线下移,呈浓度依赖。去除内皮,用一氧化氮合成酶抑制剂L-NNA、鸟苷酸环化酶抑制剂亚甲蓝、β受体阻断剂普萘洛尔、β1受体抑制剂atenolol和β2受体抑制剂ICI 118551预处理后,均可明显减弱HSYA诱导的舒张血管作用；前列腺素合成酶抑制剂吲哚美辛,K+通道抑制剂TEA、Gly、BaCl2预处理后,血管舒张作用不能被阻断。
结论：通过对血管内皮依赖性和非依赖性影响因素的研究,发现药物的舒血管活性是多途径联合作用的结果,主要经历内皮-NO-cGMP途径和β-肾上腺素受体-cAMP途径,与血管平滑肌舒张因子前列腺素I2的释放及钾离子通道无关,但能够阻断血管平滑肌的电压依赖性钙通道。
OBJECTIVE Coronary artery is the key target organ in the research of cardiovascular pharmacology, and coronary atherosclerosis cause myocardial ischemia anoxia or necrosis, plays an important role in cardiovascular diseases. Honghua is a traditional herb to promote blood circulation and remove blood stasis, hydroxysafflor yellow A is the essential water-soluble monomer component of Honghua, which is a kind of flavonoids compounds. Present study is to evaluate the vasorelaxant effect of HSYA and its possible mechanism in isolated on porcine coronary arterial ring segments.
METHODS We investigated the vasorelaxant of HSYA, pig coronary artery rings were used in experiments.
RESULTS HSYA did not change the resting tension of porcine coronary arterial ring, but showed concentration-dependent relaxant effects in PGF2a-pre-contracted coronary arteries, the two values were 124.22±6.25%(Emax) and 2.91±0.23(pD2), respectively. HSYA inhibited the KCl-induced contraction and downward shifted concentration-response curve of coronary artery rings. Removal of endothelium, incubation with L-NNA(an inhibitor of NOS), methylene blue (an inhibitor of cGMP synthesis), propranolol(β-adrenoceptor antagonist),β1-adrenoceptor antagonist atenolol, as well asβ2 -adrenoceptor antagonist ICI 118551 significantly attenuated the vaso-relaxation in porcine coronary rings induced by HSYA. However, incubation with indomethacin(an inhibitor of COX), tetraethylammonium(an inhibitor of K+ channels) did not affect the vaso-relaxation.
CONCLUSION The effect of HSYA on vasodilator may relate to activation ofβ-adrenoceptors, dependent VDCC, and endothelium-NO-cGMP pathway, but not related to PGI2 pathway and potassium channels.
结果：羟基红花黄色素A对猪冠状动脉环的静息张力无明显作用,但对预收缩的血管具有浓度依赖性舒张作用,最大舒张效应为124.22±6.25%,相应的pD2值为2.91±0.23; HSYA可使KCl的量效曲线下移,呈浓度依赖。去除内皮,用一氧化氮合成酶抑制剂L-NNA、鸟苷酸环化酶抑制剂亚甲蓝、β受体阻断剂普萘洛尔、β1受体抑制剂atenolol和β2受体抑制剂ICI 118551预处理后,均可明显减弱HSYA诱导的舒张血管作用；前列腺素合成酶抑制剂吲哚美辛,K+通道抑制剂TEA、Gly、BaCl2预处理后,血管舒张作用不能被阻断。
结论：通过对血管内皮依赖性和非依赖性影响因素的研究,发现药物的舒血管活性是多途径联合作用的结果,主要经历内皮-NO-cGMP途径和β-肾上腺素受体-cAMP途径,与血管平滑肌舒张因子前列腺素I2的释放及钾离子通道无关,但能够阻断血管平滑肌的电压依赖性钙通道。
OBJECTIVE Coronary artery is the key target organ in the research of cardiovascular pharmacology, and coronary atherosclerosis cause myocardial ischemia anoxia or necrosis, plays an important role in cardiovascular diseases. Honghua is a traditional herb to promote blood circulation and remove blood stasis, hydroxysafflor yellow A is the essential water-soluble monomer component of Honghua, which is a kind of flavonoids compounds. Present study is to evaluate the vasorelaxant effect of HSYA and its possible mechanism in isolated on porcine coronary arterial ring segments.
METHODS We investigated the vasorelaxant of HSYA, pig coronary artery rings were used in experiments.
RESULTS HSYA did not change the resting tension of porcine coronary arterial ring, but showed concentration-dependent relaxant effects in PGF2a-pre-contracted coronary arteries, the two values were 124.22±6.25%(Emax) and 2.91±0.23(pD2), respectively. HSYA inhibited the KCl-induced contraction and downward shifted concentration-response curve of coronary artery rings. Removal of endothelium, incubation with L-NNA(an inhibitor of NOS), methylene blue (an inhibitor of cGMP synthesis), propranolol(β-adrenoceptor antagonist),β1-adrenoceptor antagonist atenolol, as well asβ2 -adrenoceptor antagonist ICI 118551 significantly attenuated the vaso-relaxation in porcine coronary rings induced by HSYA. However, incubation with indomethacin(an inhibitor of COX), tetraethylammonium(an inhibitor of K+ channels) did not affect the vaso-relaxation.
CONCLUSION The effect of HSYA on vasodilator may relate to activation ofβ-adrenoceptors, dependent VDCC, and endothelium-NO-cGMP pathway, but not related to PGI2 pathway and potassium channels.
引文
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