背景:多硫酸粘多糖(MPS)被广泛用作治疗脂肪变性和血流障碍的局部制剂中的活性成分。虽然局部MPS产品可以增加皮肤血流量(CBF),潜在机制尚不清楚.
目的:在本研究中,我们旨在阐明MPS如何增加CBF。我们调查了一氧化氮(NO)的相关性,与局部血容量增加相关的强大介质,MPS在小鼠中的血流加速作用。此外,我们验证了MPS对不同皮肤细胞类型中NO产生的影响,如角质形成细胞(KCs),内皮细胞(ECs),和真皮成纤维细胞(DF)。
方法:我们使用光栅扫描光声成像介观观察体内皮肤血容量的变化。使用NO指示剂测定每个细胞中的NO产生。酶联免疫测定用于测量EC中磷酸化一氧化氮合酶(NOS)的水平,DFs,和KCs在存在或不存在MPS的情况下。
结果:局部应用MPS可增加小鼠皮肤血容量,通过添加NOS抑制剂可以消除这种增加。MPS促进各种细胞中NO的剂量依赖性产生,引起NOS磷酸化状态的改变。
结论:我们的研究结果表明,在各种皮肤细胞类型中,MPS促进皮肤血容量和NO产生的增加。这些结果表明,MPS可以通过不同皮肤细胞类型的NO生物合成途径潜在地加速CBF。
BACKGROUND: Mucopolysaccharide polysulfate (MPS) is widely used as an active ingredient in topical preparations for the treatment of asteatosis and blood flow disorders. Although topical MPS products can increase cutaneous blood flow (CBF), the underlying mechanism remains unclear.
OBJECTIVE: In this study, we aimed to elucidate how MPS increases CBF. We investigated the association of nitric oxide (NO), a powerful mediator associated with increased local blood volume, with the blood flow-accelerating action of MPS in mice. In addition, we verified the effects of MPS on NO production in different skin cell types, such as keratinocytes (KCs), endothelial cells (ECs), and dermal fibroblasts (DFs).
METHODS: We used raster-scanning optoacoustic imaging mesoscopy to observe in vivo changes in the skin blood volume. NO production was determined in each cell using an NO indicator. An enzyme-linked immunoassay was used to measure the phosphorylated nitric oxide synthase (NOS) levels in ECs, DFs, and KCs in the presence or absence of MPS.
RESULTS: Topical application of MPS increased the skin blood volume in mice, and this increase was abolished through the addition of NOS inhibitors. MPS promoted the dose-dependent production of NO in various cells, which caused alterations in the phosphorylation state of NOS.
CONCLUSIONS: Our findings demonstrate that MPS promotes an increase in skin blood volume and NO production in various skin cell types. These results suggest that MPS can potentially accelerate CBF through the NO biosynthesis pathway in different skin cell types.