复方丹参注射液对冠心病患者硝酸酯耐药的影响

目的 探讨复方丹参注射液对冠心病患者硝酸酯耐药的影响及机制。方法 将84例入选冠心病患者随机分为3组：A组(消心痛组)、B组(消心痛加复方丹参注射液组)、C组(消心痛加维生素C组)，3组消心痛用法均为15mg，每天4次，治疗时间均为10天。观察临床耐药情况、血压，分别于治疗前后用彩色多普勒检测肱动脉基础内径值(DO)、加压后肱动脉舒张反应D1，即血流介导血管内径扩张(flow-mediated vasodilation，FMD)]和含服硝酸甘油后的血管舒张反应(D2)，并采血栓测内皮素-1(endothelin-1，ET-1)、内皮源型一氧化氮合酶(endothelial nitric oxide synthase，eNOS)基因ITIRNA表达。内皮依赖性血管舒张功能(endothelial-dependent vasodilation，EDD)以(D1-DO)／DO×100％表示，非内皮依赖性血管舒张功能(endothelial-independent vasodilation，EID)以(D2-DO)／D0×100％表示。结果(1)B(28．57％)、C(35．7l％)两组临床耐药的发生率明显低于A组(64．28％)，B、C组间差异无显著性。(2)治疗后A组血压回升，与治疗前比较差异无显著性；C组虽有回升，但仍较治疗前低；B组无明显回升。B、C组间比较差异有显著性(P<0．05)。(3)治疗后A组EID降低，B、C组EDD提高(P<0．05)，B、C两组EDD、EID高于A组(P<0．05)，B组EDD高于C组(P<0．05)。(4)治疗后B组ET-1 mRNA表达下降，eNOS mRNA表达升高，c组eNOS mRNA表达也升高，与治疗前比较差异有显著性，与A组比较差异也有显著性(P<0．05)，但c组eNOS mRNA表达低于B组(P<0．05)。结论复方丹参注射液能部分阻止硝酸酯耐药的发生，优于维生素C，其机制可能与其调节eNOS、ET-1 mRNA表达及保护血管内皮功能等有关。

Effect of Compound Salvia Injection on Nitrate Ester Tolerance

OBJECTIVE: To investigate the effect and mechanism of Compound Salvia injection (CSI) on nitrate ester tolerance. METHODS: Eighty-four patients with coronary heart disease (CHD) were randomly divided into three groups, Group A treated with isosorbide dinitrate (ISD, 15 mg, 4 times per day) alone, Group B with ISD plus CSI and Group C with ISD plus vitamin C. The therapeutic course for all groups was 10 days. The tolerance to nitrate ester and blood pressure were monitored. Before and after treatment, the color Doppler ultrasonic apparatus was used to detect the baseline value of humeral arterial internal diameters (D0), the humeral arterial dilatory response under compression D1, that is, the flow-mediated vasodilation (FMD)] and the vasodilatory response after sucking of nitroglycerin (D2). And the blood levels of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS) mRNA expression were determined. The endothelial-dependent vasodilation (EDD) was expressed by (D1 - D0)/D0 x 100%, and the endothelial-independent vasodilation (EID) was expressed by (D2 - D0)/D0 x 100%. RESULTS: (1) The occurrence rate of nitrate tolerance in Group B and C (28.57% and 35.7%) was lower than that in Group A (64.29%), but insignificant difference was found between the former two. (2) After treatment, blood pressure increased in Group A to the level of pre-treatment, that in Group C also increased but still lower than that of pre-treatment, while insignificant increase was observed in Group B, comparison between Group B and C showed significant difference (P < 0.05). (3) After treatment, EID lowered in Group A, EDD increased in Group B and C (P < 0.05), EDD and EID in Group B and C were higher than those in Group A (P < 0.05), and EDD was higher in Group B than in Group C (P < 0.05). (4) After treatment, ET-1 mRNA expression lowered in Group B, eNOS mRNA expression increased in Group B and C, with significant difference as compared with those before treatment and those in Group A (P < 0.05), and eNOS mRNA expression in Group C was lower than that in Group B (P < 0.05). CONCLUSION: CSI could partially prevent the occurrence of tolerance to nitrate ester, with the effect better than vitamin C, the mechanism might be related with its regulation on eNOS, ET-1 mRNA expression and protection on vascular endothelial function.