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促进皮肤创伤愈合的新靶点:兰尼碱受体。

A novel target for the promotion of dermal wound healing: Ryanodine receptors.

机构信息

Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.

Institute of Surgical Research, University of Szeged, Szeged, Hungary.

出版信息

Toxicol Appl Pharmacol. 2019 Mar 1;366:17-24. doi: 10.1016/j.taap.2019.01.021. Epub 2019 Jan 23.

Abstract

Ryanodine receptors have an important role in the regulation of intracellular calcium levels in the nervous system and muscle. It has been described that ryanodine receptors influence keratinocyte differentiation and barrier homeostasis. Our goal was to examine the role of ryanodine receptors in the healing of full-thickness dermal wounds by means of in vitro and in vivo methods. The effect of ryanodine receptors on wound healing, microcirculation and inflammation was assessed in an in vivo mouse wound healing model, using skin fold chambers in the dorsal region, and in HaCaT cell scratch wound assay in vitro. SKH-1 mice were subjected to sterile saline (n = 36) or ryanodine receptor agonist 4-chloro-m-cresol (0.5 mM) (n = 42) or ryanodine receptor antagonist dantrolene (100 μM) (n = 42). Application of ryanodine receptor agonist 4-chloro-m-cresol did not influence the studied parameters significantly, whereas ryanodine receptor antagonist dantrolene accelerated the wound closure. Inhibition of the calcium channel also increased the vessel diameters in the wound edges during the process of healing and increased the blood flow in the capillaries at all times of measurement. Furthermore, application of dantrolene decreased xanthine-oxidoreductase activity during the inflammatory phase of wound healing. Inhibition of ryanodine receptor-mediated effects positively influence wound healing. Thus, dantrolene may be of therapeutic potential in the treatment of wounds.

摘要

兰尼碱受体在神经系统和肌肉细胞内钙离子水平的调节中起着重要作用。已经描述了兰尼碱受体影响角质形成细胞分化和屏障稳态。我们的目标是通过体外和体内方法研究兰尼碱受体在全层真皮伤口愈合中的作用。在体内小鼠伤口愈合模型中,使用背部皮肤褶皱室,以及体外 HaCaT 细胞划痕伤口测定法,评估了兰尼碱受体对伤口愈合、微循环和炎症的影响。SKH-1 小鼠接受无菌生理盐水(n=36)或兰尼碱受体激动剂 4-氯间甲酚(0.5 mM)(n=42)或兰尼碱受体拮抗剂丹曲林(100 μM)(n=42)处理。兰尼碱受体激动剂 4-氯间甲酚的应用并未显著影响研究参数,而兰尼碱受体拮抗剂丹曲林加速了伤口闭合。钙通道的抑制也在愈合过程中增加了伤口边缘的血管直径,并在所有测量时间内增加了毛细血管的血流。此外,丹曲林的应用在伤口愈合的炎症期降低了黄嘌呤氧化酶的活性。兰尼碱受体介导的作用的抑制对伤口愈合有积极影响。因此,丹曲林可能具有治疗伤口的潜在治疗作用。

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