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经阴道给予具有高细胞黏附活性的人III型胶原蛋白衍生生物材料治疗大鼠阴道萎缩

Intravaginal Administration of Human Type III Collagen-Derived Biomaterial with High Cell-Adhesion Activity to Treat Vaginal Atrophy in Rats.

作者信息

You Shuang, Liu Shuaibin, Dong Xiaojing, Li Hu, Zhu Yun, Hu Lina

机构信息

Department of Obstetrics and Gynecology, Second Affiliated Hospital, Chongqing Medical University, Linjiang Road No. 76, Chongqing 400010, China.

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

ACS Biomater Sci Eng. 2020 Apr 13;6(4):1977-1988. doi: 10.1021/acsbiomaterials.9b01649. Epub 2020 Mar 24.

Abstract

Vaginal atrophy (VA) is the thinning and drying of the vaginal walls, which can lead to a variety of symptoms. VA is usually initiated by decreasing estrogen levels in post-menopausal women; so, the traditional treatment of VA is hormone therapy (HT). Here, we sought nonhormonal therapies aimed at treating this condition safely and effectively. Collagen is an excellent biomaterial and has important biological functions in skin and mucosal tissues. In particular, collagen can bind to epithelial cells to promote proliferation and differentiation. In this study, recombinant protein T16, which was derived from human type III collagen to provide potent cell-adhesion activity, was used as a safe alternative therapy to treat VA in ovariectomy rat models. After T16 was administered intravaginally for 2 weeks, the autologous collagen arrangement was improved in the epithelium and muscle layer of the rat vagina, and the thickness of epithelium tissue also increased significantly. Compared with the sham group, collagen therapy was found to influence the expression levels of several important proteins in the vaginal tissue, resulting in the upregulation of TIMP-1, Collagen I, Collagen III, Ki-67, VEGF, and AQP-2 and the downregulation of MMP-1 and IL-6. Cells in the collagen treatment group exhibited better proliferation and less apoptosis properties. These results not only provide support for additional animal experiments to further evaluate collagen therapy in VA treatment but also suggest the potential for wide applications of collagen biomaterials with high cell-adhesion activities.

摘要

阴道萎缩(VA)是阴道壁变薄和干燥,可导致多种症状。VA通常由绝经后女性雌激素水平下降引发;因此,VA的传统治疗方法是激素疗法(HT)。在此,我们寻求旨在安全有效地治疗这种病症的非激素疗法。胶原蛋白是一种优质生物材料,在皮肤和黏膜组织中具有重要生物学功能。特别是,胶原蛋白可与上皮细胞结合以促进增殖和分化。在本研究中,源自人III型胶原蛋白以提供强大细胞黏附活性的重组蛋白T16,被用作在卵巢切除大鼠模型中治疗VA的安全替代疗法。在将T16经阴道给药2周后,大鼠阴道上皮和肌层中的自体胶原蛋白排列得到改善,上皮组织厚度也显著增加。与假手术组相比,发现胶原蛋白疗法会影响阴道组织中几种重要蛋白质的表达水平,导致TIMP-1、胶原蛋白I、胶原蛋白III、Ki-67、VEGF和AQP-2上调,以及MMP-1和IL-6下调。胶原蛋白治疗组的细胞表现出更好的增殖特性和更少的凋亡特性。这些结果不仅为进一步评估胶原蛋白疗法在VA治疗中的额外动物实验提供了支持,还表明具有高细胞黏附活性的胶原蛋白生物材料具有广泛应用的潜力。

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