Hao Mingqian, Ding Chuanbo, Sun Shuwen, Peng Xiaojuan, Liu Wencong
College of Traditional Chinese Medicine, Jilin Agricultural Science and Technology College, Jilin, People's Republic of China.
School of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, People's Republic of China.
J Inflamm Res. 2022 Aug 26;15:4921-4938. doi: 10.2147/JIR.S376692. eCollection 2022.
Diabetic ulcer remains a clinical challenge due to impaired angiogenesis and persistent inflammation, requiring new alternative therapies to promote tissue regeneration.
In this study, chitosan/sodium alginate/velvet antler blood peptides (CS/SA/VBPs) hydrogel (CAVBPH) was fabricated and used in the treatment of skin wounds in type 2 diabetes mellitus (T2D) for the first time.
VBPs were prepared by hydrolysis and ultrafiltration, and their sequences were identified using LC-MS/MS. The CAVBPH was further fabricated and characterized. A mouse model of T2D was induced by a high-sugar and high-fat diet (HSFD) and streptozotocin (STZ) injection. CAVBPH was applied topically to T2D wounds, and its effects on skin repair and potential biological mechanisms were analyzed by appearance observation, histopathological staining, bioinformatics analysis, Western blot, and 16S rRNA sequencing.
VBPs had numerous short-chain active peptides, excellent antioxidant activity, and a low hemolysis rate. CAVBPH exhibited desirable biochemical properties and participated in the diabetic wound healing process by promoting cell proliferation (PCNA and α-SMA) and angiogenesis (capillaries and CD31) and alleviating inflammation (CD68). Mechanistically, the therapeutic effect of CAVBPH on chronic wounds might rely on activating the PI3K/AKT/mTOR/HIF-1α/VEGFA pathway and reversing the expression of inflammatory cytokines TNF-α and IL-1β. The results of 16S rRNA sequencing indicated that T2D significantly altered the diversity and structure of skin flora at the wound site. CAVBPH treatment elevated the relative abundance of beneficial microbes (e.g., and ) and reversed the structural imbalance of skin microbiota.
These results indicate that CAVBPH is a promising wound dressing, and its repair effect on diabetic wounds by regulating angiogenesis, inflammatory response, and skin flora may depend on the rich small peptides in VBPs.
由于血管生成受损和炎症持续存在，糖尿病溃疡仍然是一个临床挑战，需要新的替代疗法来促进组织再生。
本研究首次制备了壳聚糖/海藻酸钠/鹿茸血肽（CS/SA/VBPs）水凝胶（CAVBPH），并将其用于治疗2型糖尿病（T2D）皮肤伤口。
通过水解和超滤制备VBPs，并使用液相色谱-串联质谱法（LC-MS/MS）鉴定其序列。进一步制备并表征CAVBPH。通过高糖高脂饮食（HSFD）和注射链脲佐菌素（STZ）诱导建立T2D小鼠模型。将CAVBPH局部应用于T2D伤口，通过外观观察、组织病理学染色、生物信息学分析、蛋白质印迹法和16S rRNA测序分析其对皮肤修复的作用和潜在生物学机制。
VBPs含有大量短链活性肽，具有优异的抗氧化活性和低溶血率。CAVBPH表现出理想的生化特性，通过促进细胞增殖（增殖细胞核抗原和α-平滑肌肌动蛋白）和血管生成（毛细血管和CD31）以及减轻炎症（CD68）参与糖尿病伤口愈合过程。从机制上讲，CAVBPH对慢性伤口的治疗作用可能依赖于激活PI3K/AKT/mTOR/HIF-1α/VEGFA通路并逆转炎性细胞因子肿瘤坏死因子-α和白细胞介素-1β的表达。16S rRNA测序结果表明，T2D显著改变了伤口部位皮肤菌群的多样性和结构。CAVBPH治疗提高了有益微生物（如 和 ）的相对丰度，逆转了皮肤微生物群的结构失衡。
这些结果表明CAVBPH是一种有前景的伤口敷料，其通过调节血管生成、炎症反应和皮肤菌群对糖尿病伤口的修复作用可能依赖于VBPs中丰富的小肽。
