通心络超微粉对大鼠络脉绌急模型的通络效应及其作用机制

Effect of Tongxinluo superfine on experimental anginal model(contraction of collaterals) in rat with endothelial dysfunction

目的:建立络脉绌急大鼠模型及探讨通心络超微粉对其的影响并初步探讨其作用机制。方法:采用蛋氨酸灌胃法复制高同型半胱氨酸血症致内皮损伤大鼠模型。取大鼠胸主动脉段进行血管舒张功能检测,并检测血浆同型半胱氨酸(Hcy)浓度、一氧化氮(NO)含量和血管性假血友病因子(vWF)水平。然后在蛋氨酸灌胃基础上予精氨酸加压素(AVP)静脉注射建立络脉绌急模型。通心络治疗组加通心络超微粉0.4 g.kg-1.d-1灌胃1周。各组记录AVP注射后标准肢体Ⅱ导联心电图30 m in。以心电图S波改变和T波压低作为心肌缺血指标。测定各组血浆NO水平,RT-PCR检测心肌内皮型一氧化氮合酶(eNOS)mRNA表达。结果:4周蛋氨酸灌胃造成大鼠高同型半胱氨酸血症;血浆vWF水平显著升高,NO水平降低,血管内皮依赖的舒张反应明显减弱,血管内皮功能受损。内皮损伤基础上给予AVP引起的S波改变和T波压低幅度都较内皮正常者严重,而通心络超微粉可减弱络脉绌急引起的S波改变和T波压低幅度。通心络组NO水平及心肌eNOS mRNA表达水平较络脉绌急组显著升高。结论:通过对内皮损伤大鼠静脉注射精氨酸加压素的方法建立了络脉绌急模型;通心络超微粉可能通过促进心肌组织eNOS mRNA表达,提高NO水平,发挥其通络效应。

Objective： To study the effect of Tongxinho superfine （TXL） on experimental anginal model induced by Arginine Vasopressin in rats with endothefial dysfunction. Method： First, the endothelial dysfunction rat model was made by methionine-induced hyperhomocysteinemia （HHcy）. The thoracic aorta were excised, and acetylcholine （Ach）-induced endothelium dependent relaxation and sodium nitroprusside （SNP） induced endothellum-independent relaxation were measured. Total plasma homocysleine （Hcy） concentrations were measured with automated fluorescence polarization immunoussay （FPIA）. Enzyme-linked immunosorbent assay （ELISA） was used to detect plasma yon Willebrand factor （vWF） level. Plasma nitric oxide （NO） contents were assayed by method of nitrate raductase. Then, the rat model of collaterals contraction （model group） was established by AVP intravenous injection in rats with endothelial dysfunction and the S wave change （AS） and T wave depression in Lead II ECG were used as the index of angina severity. The nitric oxide （NO） contents in serum and the expression of myocardinm eNOS mRNA were measured. Result： Ach （0. 1-1 000 nmol ·L^-1 ）-induced endothelium dependent relaxation （EDR） of aortic rings was significantly decreased in HHcy group. The endothelium-independent relaxation induced by SNP （0. 001-10 p.mol · L^-1 ） was not significantly different between the two groups. Plasma homocysteine concentrations and vWF levels in rats treated with methionine were higher than those of control group, while NO contents were significantly decreased in HHcy group compared with control. The results showed that L-methionine intake in- duced hyperhomocysteinemia in rats. Impaired EDR, increased vWF and decreased NO suggested the exist of endothelial dysfunction. AS of model group increased from 1 min to 5 min and T wave of model group depressed at 2 min compared with that of control after the administration of vasopressin （0.5 U · kg^ -1 ）. The intragastric administration of TXL inhibited vasopressin-induced S wave change at 4 min and 5 min and T wave depression from 30 s to 3 min after AVP injection. The NO contents in serum and the expression of myocardium eNOS mRNA of TXL group were increased compared with model group. Conclusion： Experimental angina induced by AVP injection is more severe in rats with endothelial dysfunction. Tongxinluo Superfine can protect against collaterals contraction in rats maybe by increasing the NO contents in serum and the expression of myocardium eNOS mRNA.