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丹红注射液可减轻自发性高血压大鼠的血管重构,并上调激肽释放酶-激肽系统。

Danhong injection reduces vascular remodeling and up-regulates the Kallikrein-kinin system in spontaneously hypertensive rats.

机构信息

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin, 300193, P. R. China.

Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, 220 Dongting Road, TEDA, Tianjin, 300457, P. R. China.

出版信息

Sci Rep. 2017 Jun 27;7(1):4308. doi: 10.1038/s41598-017-04661-1.

Abstract

Although Danhong injection (DHI) is one of the most prescribed cardiovascular medicines in China, its therapeutic indications and mechanisms remain partially defined. We now identify molecular targets of DHI in resistance vasculatures and demonstrate its role in vascular function and blood pressure (BP) regulation. BP was determined in DHI, Losartan, and placebo- treated Spontaneously Hypertensive Rats (SHR) by both noninvasive and invasive measurements. Vasorelaxation was examined both in conduit and resistance vasculature by ex vivo aortic rings. Microarray analysis was performed and gene expression changes were verified by RT-qPCR and ELISA. Diastolic, systolic and mean BPs were significantly lower in DHI-treated SHR than controls by both tail-cuff and invasive BP measurements. In ex vivo rings, aortic and mesenteric vessels from SHR treated with DHI exhibited significantly greater acetylcholine-mediated relaxation. Among the 282 genes that are differentially expressed in microarray analysis, DHI treatment up-regulated the expression of kallikrein and plasma kallikrein B genes. DHI also significantly increased serum kallikrein content in SHR. Treatment with DHI significantly increased the ratio of aortic lumen to outer diameter. Therefore, the reduction of vascular remodeling and the up-regulation of Kallikrein-kinin system contribute, at least in part, to the antihypertensive effect of DHI in SHR.

摘要

丹红注射液(DHI)是中国应用最广泛的心血管药物之一,但它的治疗适应证和作用机制尚不完全明确。本研究旨在探讨 DHI 在阻力血管中的作用靶点及其对血管功能和血压(BP)的调节作用。通过非侵入性和侵入性测量方法,检测 DHI、氯沙坦和安慰剂治疗的自发性高血压大鼠(SHR)的 BP。通过离体主动脉环检测 DHI 在管腔和阻力血管中的血管舒张作用。采用微阵列分析,通过 RT-qPCR 和 ELISA 验证基因表达变化。通过尾套和侵入性 BP 测量,DHI 治疗的 SHR 的舒张压、收缩压和平均 BP 明显低于对照组。在离体环中,DHI 治疗的 SHR 的主动脉和肠系膜血管对乙酰胆碱介导的舒张作用明显增强。在微阵列分析中差异表达的 282 个基因中,DHI 治疗上调激肽释放酶和血浆激肽释放酶 B 基因的表达。DHI 还显著增加了 SHR 中的血清激肽含量。DHI 治疗显著增加了主动脉腔与外径的比值。因此,血管重构的减少和激肽释放酶-激肽系统的上调至少部分解释了 DHI 在 SHR 中的降压作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/412f/5487322/9f884dd64192/41598_2017_4661_Fig1_HTML.jpg

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