通心络对大鼠颈总动脉外膜慢性损伤诱导的血管收缩的影响。

Effect of tongxinluo on vasoconstriction induced by the chronic injury of the adventitia in the rat carotid artery.

机构信息

Cardiology Department, The First Affiliated Hospital of China Medical University, Heping District, Shenyang, China.

出版信息

J Ethnopharmacol. 2010 Sep 15;131(2):300-5. doi: 10.1016/j.jep.2010.06.037. Epub 2010 Jun 30.

DOI:10.1016/j.jep.2010.06.037

PMID:20600751

Abstract

OBJECTIVE

Tongxinluo (TXL) is a traditional Chinese medicine that is developed on the meridian theory of traditional Chinese medicine, with the function of alleviating the angina. The present study was undertaken to explore the molecular mechanism of TXL in treating the pectoris angina through observing the effectiveness of TXL superfine powder on the vasoconstriction and the activation of RhoA/Rho-kinase pathway induced by the injury of the adventitia.

METHODS

36 male Wistar Kyoto rats were assigned to 3 treatments (n=12): vehicle, TXL (400 mg kg(-1) day(-1)) and fasudil (15 mg kg(-1) day(-1)). After 1 week of treatment, adventitia injury was induced by positioning a silicone collar around the right carotid artery for 1 week. Blood flow and vascular reactivity to serotonin were determined 1 week after injurying, the both sides of carotids were harvested for morphometry, Western blotting analysis and RT-PCR analysis.

RESULTS

Adventitia injury leaded to histological changes of vasoconstriction with the lumen cross-sectional area of 44.7% (p<0.001) decreasing and the media diameter of 62.31% (p<0.001) increasing, accompanying by the reduction of the blood flow and the increase of vascular reactivity sensitivity to serotonin. Treatment with both TXL superfine powder and fasudil can prevent the development of vasoconstriction, improve the carotid blood flow and normalize the vascular hypersensitivity to serotonin. Adventitia injuring of the rat carotid increased the expression of Rho-kinase mRNA and p-MYPT1(Thr696) protein by 1.78-fold (p<0.05) and >2-fold respectively (p<0.05). TXL reduced the expression of Rho-kinase mRNA and p-MYPT1(Thr696) protein by 54.2% (p<0.05) and 57.1% (p<0.05) respectively in collared arteries. Fasudil restrained the p-MYPT1(Thr696) protein expression by 63.8% (p<0.05) in collared arteries, did not affect the collar-induced the increase of Rho-kinase mRNA expression (p>0.05).

CONCLUSIONS

Treatment with TXL, similar to that with fasudil, can effectively prevent collar-induced vasoconstriction and vascular hyperreactivity to serotonin through inhibiting the RhoA/Rho-kinase pathway.

摘要

目的

通心络（TXL）是一种基于中医经络理论开发的中药，具有缓解心绞痛的作用。本研究旨在通过观察 TXL 超微粉对动脉外膜损伤引起的血管收缩和 RhoA/Rho-激酶通路激活的影响，探讨 TXL 治疗心绞痛的分子机制。

方法

36 只雄性 Wistar Kyoto 大鼠随机分为 3 组（每组 12 只）：对照组、TXL（400mg/kg·d）组和法舒地尔（15mg/kg·d）组。经过 1 周的治疗，用硅酮环定位右颈动脉 1 周造成动脉外膜损伤。损伤后 1 周测定血流和血管对 5-羟色胺的反应性，取颈总动脉两侧进行形态学、Western blot 分析和 RT-PCR 分析。

结果

动脉外膜损伤导致血管收缩的组织学变化，管腔横截面积减少 44.7%（p<0.001），中膜直径减少 62.31%（p<0.001），同时伴有血流减少和对 5-羟色胺血管反应性增加。TXL 超微粉和法舒地尔治疗均可预防血管收缩的发生，改善颈总动脉血流，使对 5-羟色胺的血管高反应性正常化。大鼠颈动脉外膜损伤使 Rho-激酶 mRNA 和 p-MYPT1（Thr696）蛋白表达增加 1.78 倍（p<0.05）和 >2 倍（p<0.05）。TXL 可使环扎动脉中 Rho-激酶 mRNA 和 p-MYPT1（Thr696）蛋白表达分别减少 54.2%（p<0.05）和 57.1%（p<0.05）。法舒地尔抑制环扎动脉中 p-MYPT1（Thr696）蛋白表达 63.8%（p<0.05），但不影响 Rho-激酶 mRNA 表达的增加（p>0.05）。