Stachydrine protects eNOS uncoupling and ameliorates endothelial dysfunction induced by homocysteine.
Stachydrine protects eNOS uncoupling and ameliorates endothelial dysfunction induced by homocysteine.
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水苏碱保护 eNOS 解偶联并改善同型半胱氨酸诱导的内皮功能障碍
DOI：
10.1186/s10020-018-0010-0
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发表时间：
2018-03-19
期刊：
影响因子：
--
通讯作者：
Wang N
中科院分区：
文献类型：
--
作者：
Xie X;Zhang Z;Wang X;Luo Z;Lai B;Xiao L;Wang N
高同型半胱氨酸血症（HHcy）是心血管疾病（CVD）的独立危险因素。水苏碱（Stachydrine，STA）是益母草中的一种有效成分，广泛用于妇科和心血管疾病。本研究旨在探讨STA对同型半胱氨酸（Hcy）诱导的内皮功能障碍的影响。用多功能肌电描记系统测定了STA对大鼠胸主动脉（TA）、肠系膜动脉（MA）和肾动脉（RA）的舒张作用。测定一氧化氮（NO）、四氢生物蝶呤（BH 4）和环磷酸鸟苷（cGMP）的含量。采用Western印迹法检测内皮型一氧化氮合酶（eNOS）二聚体和单体的表达。通过定量逆转录酶-PCR（qRT-PCR）和Western印迹法测定GTP环化水解酶1（GTPCH 1）和二氢叶酸还原酶（DHFR）的表达。STA能有效地阻断同型半胱氨酸对TA、MA和RA大鼠血管内皮依赖性舒张功能的损害。NOS抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）或NO敏感性鸟苷酸环化酶抑制剂1H- [1，2，4]恶二唑并[4，3-a]喹喔啉-1-酮（ODQ）可减少STA引起的动脉松弛，但诱导型iNOS抑制剂1400 W和非选择性考克斯抑制剂消炎痛均不减少STA引起的动脉松弛。同型半胱氨酸引起eNOS解偶联，NO、cGMP和BH_4含量降低，STA可减弱上述作用。此外，STA阻止了Hcy处理的BAEC中GTPCH 1和DHFR水平的降低。我们证明STA通过增加GTPCH 1和DHFR的表达，有效地逆转了Hcy诱导的内皮功能障碍，并防止eNOS解偶联。这些结果揭示了STA发挥其有益血管效应的新机制。本文的在线版本（10.1186/s10020-018-0010-0）包含补充材料，可供授权用户使用。
Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases (CVDs). Stachydrine (STA) is an active component in Chinese motherwort Leonurus heterophyllus sweet, which has been widely used for gynecological and cardiovascular disorders. This study is aimed to examine the effects of STA on homocysteine (Hcy)-induced endothelial dysfunction. The effects of STA on vascular relaxation in rat thoracic aortas (TA), mesenteric arteries (MA) and renal arteries (RA) were measured by using Multi Myograph System. The levels of nitric oxide (NO), tetrahydrobiopterin (BH4) and guanosine 3′, 5′ cyclic monophosphate (cGMP) were determined. Endothelial nitric oxide synthase (eNOS) dimers and monomers were assayed by using Western blotting. GTP cyclohydrolase 1 (GTPCH1) and dihydrofolate reductase (DHFR) expressions were measured by using quantitative reverse transcriptase-PCR (qRT-PCR) and Western blotting. STA effectively blocked Hcy-induced impairment of endothelium-dependent vasorelaxation in rat TA, MA and RA. STA-elicited arterial relaxations were reduced by NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or the NO-sensitive guanylyl cyclase inhibitor 1H- [1, 2, 4] Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), but not by inducible iNOS inhibitor 1400 W nor the nonselective COX inhibitor indomethacin. Hcy caused eNOS uncoupling and decreases in NO, cGMP and BH4, which were attenuated by STA. Moreover, STA prevented decreases of GTPCH1 and DHFR levels in Hcy-treated BAECs. We demonstrated that STA effectively reversed the Hcy-induced endothelial dysfunction and prevented eNOS uncoupling by increasing the expression of GTPCH1 and DHFR. These results revealed a novel mechanism by which STA exerts its beneficial vascular effects. The online version of this article (10.1186/s10020-018-0010-0) contains supplementary material, which is available to authorized users.
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7.3
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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