蜂胶总黄酮的舒血管效应及其机制探讨

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (11): 1227-1232.

蜂胶总黄酮的舒血管效应及其机制探讨

王海华, 曾瑾, 崔凤娟, 王海珍, 周萍萍, 王静

皖南医学院生理教研室,芜湖 241002,安徽

收稿日期:2014-04-11 修回日期:2014-10-23 出版日期:2014-11-26 发布日期:2014-12-09
通讯作者: 王海华,男,副教授,硕士生导师,研究方向:痛觉及其调制、心血管病理生理学。Tel: 13675536187 E-mail: wanghaihua9972@sina.com
作者简介:曾瑾,并列第一作者,女,硕士研究生。Tel: 15855975153 E-mail: mabelwanyi@126.com
基金资助:
安徽省高校省级科学研究重点项目(KJ2013A251); 皖南医学院重点科研项目培育基金(WK2012Z01); 安徽省2012年省级教学研究重点项目(2012JYXM313); 活性生物大分子研究安徽省重点实验室(科基[2012]126号)

Vasodilator effects and its mechanism of total flavonoids of Propolis in rats

WANG Hai-hua, ZENG Jin, CUI Feng-juan, WANG Hai-zhen, ZHOU Ping-ping, WANG Jing

Department of Physiology, Wannan Medical College, Wuhu 241002, Anhui,China

Received:2014-04-11 Revised:2014-10-23 Online:2014-11-26 Published:2014-12-09

摘要/Abstract

摘要： 目的探讨蜂胶总黄酮(total flavonoids of propoli,TFP)对大鼠的胸主动脉舒张作用及其可能作用机制。方法 SD雄性大鼠随机分为4组(n=6):即对照组(CG),TFP低、中、高剂量(50、100、200 mg/kg)组(即LG、MG和HG组),各组大鼠按TFP低、中、高剂量等容积灌胃(1次/d),CG大鼠等容积生理盐水灌胃(1次/d),连续4周。主动脉取血3~5 mL 测量血小板聚集率,制备离体胸主动脉环,经生物信号采集分析系统记录主动脉环张力变化,观察各组大鼠血管环对去氧肾上腺注射液(PE)和KCl刺激的收缩反应,同时检测各组大鼠胸主动脉环匀浆一氧化氮(NO)含量及诱导型一氧化氮合酶(iNOS)活性。结果与CG组相比,TFP呈剂量依赖性抑制大鼠血小板聚集率;对内皮完整的主动脉环,在KCl(12~60 mmol/L)预收缩的基础上,TFP呈剂量依赖性舒张作用;在PE(1×10^-6 mol/L)预收缩的基础上,TFP也呈剂量依赖性改善乙酰胆碱(ACh)(1×10^-8~1×10^-5 mol/L)的舒张效应;非选择性一氧化氮合酶(NOS)抑制剂N-硝基-L-精氨酸甲酯(L-NAME) (10^-4 mol/L)或环氧合酶抑制剂吲哚美辛(Indo,10^-5 mol/L)预孵育后,TFP对PE(10^-8~10^-5 mol/L)诱导下的各组血管环的收缩反应均增强。生化检查结果显示,与CG组相比,TFP呈剂量依赖性提高胸主动脉环iNOS活性和NO含量。结论 TFP呈剂量依赖性抑制大鼠血小板聚集率;TFP剂量依赖性改善大鼠血管的舒张功能,提示其舒张效应是通过改善血管内皮细胞功能及阻滞电压门控Ca²⁺通道有关,改善血管内皮细胞功能可能是使其增加释放NO和前列环素(PGI₂)实现的,至于其阻滞Ca²⁺通道机制有待进一步探讨。

关键词: 蜂胶总黄酮, 胸主动脉环, 内皮细胞, 血管舒张

Abstract: AIM: To investigate the vasorelaxant effects of total flavonoids of propoil(TFP) on isolated thoracic aorta of rats and its mechanism. METHODS: 30 male SD rats were randomly divided into four groups(n=6 each): saline control group(CG), low-, middle- and high-dose total flavonoids of propoil group(LG, MG, HG, respectively). Rats in LG, MG and HG were intragastrically (i.g) given TFP at doses with equal volume(qd), Rats in CG group were given equal volume normal saline(i.g, qd). For 4 consecutive weeks, 3-5 mL blood samples were obtained from the aorta and platelet aggregation was measured. Study was performed with the model of isolated rat thoracic aorta rings in organ bath, and the contractile reaction was observed by Phenylephrine hydrochloride injection(PE) and KCl in isolated thoracic aorta of each group.The content of Nitric oxide(NO) and the activity of inducible nitric oxide synthase(iNOS) were detected in isolated thoracic aorta of each group. RESULTS: Compared with the CG group, TFP showed a dose-dependent inhibition on the rate of platelet aggregation in rats, and a dose-dependent relaxation on the aorta rings with endothelium on the basis of pre-contracted of KCl(12-60 mmol/L); TFP improved the relaxation effect of Ach (1×10^-8-1×10^-5 mol/L) of the aorta rings on the basis of pre-contracted of PE(1×10^-6 mol/L); After pretreatment with non-selective nitric oxide synthase (NOS) inhibitor L-NAME or cyclooxygenase inhibitor indomethacin (Indo), PE(10^-8-10^-5 mol/L) induced contractile reaction of isolated thoracic aorta of TFP groups were all enhanced.Compared with the CG group, TFP showed a dose-dependent improvement with iNOS activity and NO content of thoracic aortic rings. CONCLUSION: TFP has dose-dependent inhibition on the platelet aggregation in rats and dose-dependent improvement on the relaxation of isolated rat thoracic aorta rings. Its relaxation effect is through improvement of endothelial function and the inhibition of voltage-operated calcium channels, and the function of improved endothelial function may through an increase in release of NO and prostacyclin (PGI₂). As for the mechanism of inhibition of Ca²⁺ channels, it needs further exploration.

Key words: total flavonoids of propoil(TFP), thoracic aorta rings, endothelial cell, vasodilation

中图分类号:

R965.2

王海华, 曾瑾, 崔凤娟, 王海珍, 周萍萍, 王静. 蜂胶总黄酮的舒血管效应及其机制探讨[J]. 中国临床药理学与治疗学, 2014, 19(11): 1227-1232.

WANG Hai-hua, ZENG Jin, CUI Feng-juan, WANG Hai-zhen, ZHOU Ping-ping, WANG Jing. Vasodilator effects and its mechanism of total flavonoids of Propolis in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(11): 1227-1232.

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