基于蜘蛛丝蛋白、丝素蛋白和丝胶蛋白的乳膏在体内皮肤修复性再生中的应用

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论证修复性再生过程的障碍会导致细胞外基质形成不足，从而引发慢性创面，这类伤口通常需要个体化的治疗策略。 在现代再生医学中，丝蛋白等生物高分子因其独特性质被广泛用于敷料基材及药物递送系统。蜘蛛丝蛋白（spidroin）、丝素蛋白（fibroin）和丝胶蛋白（sericin）具有良好的生物相容性，能够调节细胞内信号通路，并具有抗菌活性，因此被视为潜在的创面愈合治疗材料。

目的。评估含有spidroin、fibroin和sericin混合丝蛋白溶液的乳膏对大鼠皮肤再生的影响。

材料与方法。以30只雄性大鼠为研究对象，在其背部制备直径为20mm的全层皮肤切除缺损，并将其随机分为实验组和两个对照组。实验组每日外敷所研制的丝蛋白乳膏；第一对照组每日使用5%右泛醇（dexpanthenol）；第二对照组则不进行任何处理，自然愈合。通过创面面积测量、组织形态计量分析以及临床血液学检查，评估皮肤的修复过程及机体的反应性变化。

结果。与自然愈合组相比，实验组使用丝蛋白乳膏可显著加快创面愈合速度，大鼠皮肤于第14天实现完全再生。炎症活动评估显示，血液学分析中未见明显异常（仅出现轻度粒细胞增多和急性失血性贫血表现），且免疫细胞浸润程度低于对照组。

结论。蜘蛛丝蛋白（spidroin）与昆虫丝蛋白（fibroin和sericin）的组合可增强细胞的迁移、增殖与分化，促进细胞外基质的形成，并具有抗炎作用，同时不具有免疫原性。上述特性表明，该蛋白组合有望作为治疗病理性创面愈合障碍的药物，并具备临床应用潜力。

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作者简介

Irina Sorochanu

North-Western State Medical University named after I.I. Mechnikov

编辑信件的主要联系方式.
Email: opeairina@gmail.com
ORCID iD: 0000-0002-6909-8937
SPIN 代码: 4072-3845
俄罗斯联邦, 41 Kirochnaja st, 191015, Saint Petersburg

Kristina S. Blitzine

North-Western State Medical University named after I.I. Mechnikov

Email: kristina.blitsyn@gmail.com
ORCID iD: 0000-0002-2347-0123
SPIN 代码: 8210-8836
俄罗斯联邦, 41 Kirochnaja st, 191015, Saint Petersburg

Dauddin I. Daudi

Saint-Petersburg National Research University of Information Technologies, Mechanics and Optics; Silkins LLC

Email: d.daudi@patentcore.ru
ORCID iD: 0000-0003-2413-3695
SPIN 代码: 2765-0230
俄罗斯联邦, Saint Petersburg; Moscow

Nikita I. Zhemkov

North-Western State Medical University named after I.I. Mechnikov

Email: zhemkovni@gmail.com
ORCID iD: 0009-0003-2423-6544
SPIN 代码: 3779-4360
俄罗斯联邦, 41 Kirochnaja st, 191015, Saint Petersburg

Alina A. Pechenina

North-Western State Medical University named after I.I. Mechnikov

Email: alina.kyzminap@gmail.com
ORCID iD: 0009-0003-7964-1256
SPIN 代码: 8920-9532
俄罗斯联邦, 41 Kirochnaja st, 191015, Saint Petersburg

Maria A. Dmitrieva

Saint-Petersburg National Research University of Information Technologies, Mechanics and Optics; Silkins LLC

Email: m_dmitrieva@scamt-itmo.ru
ORCID iD: 0009-0006-1596-3899
俄罗斯联邦, Saint Petersburg; Moscow

Nikita A. Grin

Silkins LLC; Stavropol State Medical University

Email: nikita.grin.2014@mail.ru
ORCID iD: 0009-0000-4145-7160
SPIN 代码: 5964-9291
俄罗斯联邦, Moscow; Stavropol

Tatevik T. Asatryan

North-Western State Medical University named after I.I. Mechnikov

Email: Tatevik.asatryan@szgmu.ru
ORCID iD: 0000-0002-9146-3080
SPIN 代码: 5587-1360

MD, Cand. Sci. (Medicine), Assistant Professor

俄罗斯联邦, 41 Kirochnaja st, 191015, Saint Petersburg

Vladislav V. Tatarkin

North-Western State Medical University named after I.I. Mechnikov

Email: vladislav.tatarkin@szgmu.ru
ORCID iD: 0000-0002-9599-3935
SPIN 代码: 5008-4677

MD, Cand. Sci. (Medicine), Assistant Professor

俄罗斯联邦, 41 Kirochnaja st, 191015, Saint Petersburg

Evgeniy M. Trunin

North-Western State Medical University named after I.I. Mechnikov

Email: evgeniy.trunin@szgmu.ru
ORCID iD: 0000-0002-2452-0321
SPIN 代码: 5903-0288

MD, Dr. Sci. (Medicine), Professor

俄罗斯联邦, 41 Kirochnaja st, 191015, Saint Petersburg

Roman V. Deev

Petrovsky National Research Centre Of Surgery

Email: romdey@gmail.com
ORCID iD: 0000-0001-8389-3841
SPIN 代码: 2957-1687

MD, Cand. Sci. (Medicine), Assistant Professor

俄罗斯联邦, Moscow

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2. Fig. 1. Wound closure assessment: the black dashed line represents the initial wound area (at day 0, S0), and the red dashed line indicates the wound area at the control time point (Sx). Wound closure was calculated as the ratio of the closed wound area to its initial area, expressed as a percentage.

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3. Fig. 2. Planimetric wound analysis: а, wound healing and epithelialization changes under the influence of the test cream, dexpanthenol, and natural healing (control) at different time points; b, wound closure changes (the graph presents median values, with a statistically significant difference between the experimental and control groups observed on day 7, p = 0.010).

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4. Fig. 3. Histological examination of regenerating tissue in rats from different groups: а, histotopograms of the damaged areas and surrounding healthy tissues, stained with hematoxylin and eosin, ×40 (#, granulation tissue; |, boundary between the wound defect and the keratinocyte proliferation zone with epithelial layer growth; ↑, restoration of skin appendages; *, complete wound closure); b, changes of linear defect size, determined as the distance between the boundaries of epithelial growth zones (data presented as Me [Q1; Q3], where Me is the median, Q1 is the first quartile, and Q3 is the third quartile); с, inflammatory response intensity assessment using a semi-quantitative 4-point scale (0 points, no inflammation; 1–4 points, wound infiltration by inflammatory cells covering <25%, 25–50%, 50–75%, and >75% of the area, respectively).

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5. Appendix 1. Changes of laboratory parameters in clinical blood tests of rats in different groups
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