Molecular mechanism of Chuanxiong Rhizoma in treating coronary artery diseases.

Molecular mechanism of Chuanxiong Rhizoma in treating coronary artery diseases.
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川芎治疗冠心病的分子机制

DOI:
10.1016/j.chmed.2021.03.001
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发表时间:
2021-07
影响因子:
3.8
通讯作者:
--
中科院分区:
其他
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目前,对黄芪(CR)的研究主要集中在L-精氨酸-一氧化氮(NO)途径,而对硝酸盐-亚硝酸盐-NO(NO3−-NO2−-NO)途径的研究较少。因此,本研究的目的是评价CR在冠状动脉疾病(CAD)中的作用和作用机制。在NO3−-NO2−-NO途径中检测NO3−、NO2−和NO水平。使用高效离子色谱法定量NO3−和NO2−水平。然后,使用具有荧光探针的多功能酶标记物定量NO。用多功能肌张力仪测量主动脉环张力。CR中NO3-含量高,NO2-含量低,在内源性还原酶存在下可有效地将NO3-转化为NO2-。将人冠状动脉内皮细胞(HCAECs)与含CR的血清一起孵育,结果表明,在缺氧条件下,CR显著降低了细胞中NO3−的含量,并增加了NO2−和NO的水平。此外,CR显着放松孤立的主动脉环时,L-精氨酸-NO通路被阻断。CR的最佳松弛浓度为200 mg/mL。CR补充细胞和血管中的大量NO,通过NO3−-NO2−-NO途径实现舒张,从而弥补l-精氨酸-NO途径被抑制后NO缺乏所造成的不足。这项研究也支持了传统中药在未来药物开发中的潜在用途。
Most of the studies on the herb Chuanxiong Rhizoma (CR) have focused on the l-arginine-nitric oxide (NO) pathway, but the nitrate-nitrite-NO (NO3−–NO2−–NO) pathway was rarely investigated. Therefore, the aim of this study was to evaluate the effects and mechanisms of action of CR in coronary artery disease (CAD). The NO3−, NO2− and NO levels were examined in the NO3−–NO2−–NO pathway. High-performance ion chromatography was used to quantify NO3− and NO2− levels. Then, NO was quantified using a multifunctional enzyme marker with a fluorescent probe. The tension of aortic rings was measured using a multi myograph system. High content of NO3− and low content of NO2− was found in CR, and which could potently convert NO3− to NO2− in the presence of endogenous reductase enzyme. Incubating human coronary artery endothelial cells (HCAECs) with CR-containing serum showed that CR significantly decreased the NO3− content and increased the levels of NO2− and NO in the cells under hypoxic conditions. In addition, CR significantly relaxed isolated aortic rings when the l-arginine –NO pathway was blocked. The optimal concentration of CR for relaxation was 200 mg/mL. CR supplements large amounts of NO in cells and vessels to achieve relaxation via the NO3−–NO2−–NO pathway, thereby making up for the deficiency caused by the lack of NO after the l-arginine-NO pathway is suppressed. This study also supports the potential use of a traditional Chinese herb for future drug development.