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邓氏通冠胶囊改善缺血心肌供血的时效量效关系及NO机制研究 被引量:12

Time-effect and Dose-effect Relationship of Professor Deng's Tongguan Capsule in Improving Blood Supply of Ischemic Myocardium and Its Nitric Oxide Mechanism
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摘要 【目的】观察邓氏通冠胶囊改善心肌缺血的时效、量效关系及其NO机制。【方法】时效实验中,昆明种小鼠随机分为6组,即正常对照组、模型组、4个通冠胶囊组(中药组,分别用药1、3、5、7 d,剂量为0.5 g/kg);量效实验中,小鼠随机分为正常对照组、模型组、4个通冠胶囊组(中药组,剂量分别为0.25、0.5、1、2 g/kg);除正常对照组外,其他组均采用腹腔注射垂体后叶素(Pit,30 U/kg)复制心肌缺血模型,测量60 min内心电图T波变化,采用酶法测定小鼠血浆NO含量以确定最佳有效剂量和用药时间;采用免疫组化法测定小鼠心肌一氧化氮合酶(eNOS)活性,采用逆转录聚合酶链反应检测小鼠心肌eNOS基因表达。【结果】在用药3 d后即达到改善心肌缺血的最佳疗效,有效剂量为0.5 g/kg。通冠胶囊能显著性升高心肌缺血小鼠的血浆NO含量与心肌细胞内的eNOS活性,提高缺血心肌eNOS mRNA的表达(均P<0.05)。【结论】邓氏通冠胶囊可能是通过提高eNOS基因的表达,增强eNOS的活性,从而升高NO水平而达到改善缺血心肌供血作用的。 [Objective] To observe the time-effect and dose-effect relationship of Professor Deng's Tongguan Capsule (PDTC, mainly composed of Radix Astragali, Radix Salviae Miltiorrhizae, Hirudo, Borneolum Syntheticum) in improving blood supply of ischemic myocardium and to explore its nitric oxide (NO) mechanism. [Methods] In timeeffect experiment, Kunm/ng mice were randomized into normal control group, model group and four PDTC groups (in the dose of 0.5 g/kg for 1, 3, 5 and 7 days respectively). In dose-effect experiment, mice were randomized into normal control group, model group and four PDTC groups (in the dose of 0.25, 0.5, 1 and 2 g/kg respectively). Except the normal control group, the mice in other groups received intraperitoneal injection of pituitrin (30 U/kg) to induce myocardial ischemia. The voltage changes of T wave in electrocardiogram within 60min were measured. Mice plasma NO content was detected by enzyme method, thus to explore the optimal dosage and administration time. Immunohistochemical method was used to detect mice myocardial endothelial NO synthase (eNOS) and reverse transcriptase polymerase chain reaction (RT-PCR) was applied to examine mice myocardial eNOS gene expression. [Results] The best therapeutic effect was achieved after 3-day treatment with PDTC, and the effective dose is 0.5 g/kg. In this dose, PDTC obviously increased plasma NO content in myocardial ischemia mice, and elevated eNOS activity and eNOS mRNA expression in rat ischemic myocardium ( P 〈 0.05 compared with the model group). [ Conclusion ] PDTC in the dose of 0.5 g/kg for consecutive 3 days can effectively improve myocardial ischemia, and its mechanism may be related to the increase of eNOS gene expression and enhancement of eNOS activity, thus increase plasma NO content.
出处 《广州中医药大学学报》 CAS 2007年第4期301-305,共5页 Journal of Guangzhou University of Traditional Chinese Medicine
基金 广东省中医药局科研课题(编号:1050168)
关键词 邓氏通冠胶囊/药理学 心肌缺血/中药疗法 心肌/病理学 基因表达调控 疾病模型 动物 小鼠 PROFESSOR DENG'S TONGGUAN CAPSULE/pharmacology MYOCARDIAL ISCHEMIA/TCD therapy MYOCARDIUM/pathology GENE EXPRESSION REGULATION DISEASE MODELS, ANIMAL MICE
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