Department of Clinical Anatomy and Operative Surgery, Department of Pathological Anatomy, Institute for Regenerative Medicine, Sechenov University, 8/1 Trubetzkaya Street, 119991 Moscow, Russia.
Department of Morphology, National Research Nuclear University MEPHI, 31 Kashirskoe Highway, 115409 Moscow, Russia.
Biomolecules. 2021 Jun 3;11(6):834. doi: 10.3390/biom11060834.
The main goal of our study was to explore the wound-healing property of a novel cerium-containing N-acethyl-6-aminohexanoate acid compound and determine key molecular targets of the compound mode of action in diabetic animals.
Cerium N-acetyl-6-aminohexanoate (laboratory name LHT-8-17) as a 10 mg/mL aquatic spray was used as wound experimental topical therapy. LHT-8-17 toxicity was assessed in human skin epidermal cell culture using (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A linear wound was reproduced in 18 outbred white rats with streptozotocin-induced (60 mg/kg i.p.) diabetes; planar cutaneous defect was modelled in 60 C57Bl mice with streptozotocin-induced (200 mg/kg i.p.) diabetes and 90 diabetic / mice. Firmness of the forming scar was assessed mechanically. Skin defect covering was histologically evaluated on days 5, 10, 15, and 20. Tissue TNF-α, IL-1β and IL-10 levels were determined by quantitative ELISA. Oxidative stress activity was detected by Fe-induced chemiluminescence. Ki-67 expression and CD34 cell positivity were assessed using immunohistochemistry. gene expression was detected by real-time PCR. LHT-8-17 anti-microbial potency was assessed in wound tissues contaminated by MRSA.
LHT-8-17 4 mg twice daily accelerated linear and planar wound healing in animals with type 1 and type 2 diabetes. The formulated topical application depressed tissue TNF-α, IL-1β, and oxidative reaction activity along with sustaining both the IL-10 concentration and antioxidant capacity. LHT-8-17 induced Ki-67 positivity of fibroblasts and pro-keratinocytes, upregulated gene expression, and increased tissue vascularization. The formulation possessed anti-microbial properties.
The obtained results allow us to consider the formulation as a promising pharmacological agent for diabetic wound topical treatment.
我们研究的主要目标是探索一种新型含铈 N-乙酰-6-氨基己酸化合物的伤口愈合特性，并确定该化合物在糖尿病动物中的作用模式的关键分子靶点。
将铈 N-乙酰-6-氨基己酸（实验室名称为 LHT-8-17）作为 10mg/mL 水喷雾用于伤口实验性局部治疗。使用（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴化物（MTT）测定法在人皮肤表皮细胞培养物中评估 LHT-8-17 的毒性。在 18 只通过链脲佐菌素（60mg/kg ip）诱导糖尿病的杂种白色大鼠中重现线性伤口；在 60 只通过链脲佐菌素（200mg/kg ip）诱导糖尿病和 90 只糖尿病 / 小鼠中建立平面皮肤缺损模型。通过机械评估形成的疤痕的硬度。在第 5、10、15 和 20 天对皮肤缺损覆盖进行组织学评估。通过定量 ELISA 测定组织 TNF-α、IL-1β 和 IL-10 水平。通过 Fe 诱导的化学发光检测氧化应激活性。使用免疫组织化学评估 Ki-67 表达和 CD34 细胞阳性率。通过实时 PCR 检测 基因表达。评估 LHT-8-17 在受 MRSA 污染的伤口组织中的抗微生物效力。
LHT-8-17 每天两次 4mg 可加速 1 型和 2 型糖尿病动物的线性和平面伤口愈合。该配方的局部应用可降低组织 TNF-α、IL-1β 和氧化反应活性，同时维持 IL-10 浓度和抗氧化能力。LHT-8-17 诱导成纤维细胞和前角质形成细胞的 Ki-67 阳性，上调 基因表达，并增加组织血管化。该配方具有抗微生物特性。
获得的结果使我们能够将该配方视为治疗糖尿病伤口的有前途的药理学药物。
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