中国组织工程研究

中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (3): 360-366.doi: 10.12307/2023.045

• 纳米生物材料 nanobiomaterials • 上一篇    下一篇

制备金丝桃苷纳米粒修复子宫内膜损伤

李  玥1，吕  妍1，冯婉莹1，宋  阳2，闫  语2，关永格3   

  1. 1广州中医药大学第三临床医学院，广东省广州市  510006；2广州中医药大学护理学院，广东省广州市  510006；3广州中医药大学第三附属医院，广东省广州市  510240
  • 收稿日期:2022-01-15 接受日期:2022-03-10 出版日期:2023-01-28 发布日期:2022-05-20
  • 通讯作者: 宋阳，博士生导师，广州中医药大学护理学院，广东省广州市 510006
  • 作者简介:李玥，女，1996年生，山东省济南市人，汉族，硕士，主要从事中医药防治女性生殖障碍及妇科杂病研究。
  • 基金资助:
    国家自然科学基金面上项目(81873331)，项目参与者：关永格；广东省自然科学基金面上项目(2020A151501757)，项目负责人：关永格；广东省自然科学基金面上项目(2021A1515011435)，项目负责人：宋阳

Preparation of hyperoside nanoparticles to repair endometrial injury

Li Yue1, Lyu Yan1, Feng Wanying1, Song Yang2, Yan Yu2, Guan Yongge3   

  1. 1The Third Clinical College of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510006, Guangdong Province, China; 2School of Nursing of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510006, Guangdong Province, China; 3The Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510240, Guangdong Province, China
  • Received:2022-01-15 Accepted:2022-03-10 Online:2023-01-28 Published:2022-05-20
  • Contact: Song Yang, Doctoral supervisor, School of Nursing of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510006, Guangdong Province, China
  • About author:Li Yue, Master, The Third Clinical College of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510006, Guangdong Province, China
  • Supported by:
    National Natural Science Foundation of China (General Program), No. 81873331 (to GYG); General Project of Natural Science Foundation of Guangdong Province, No. 2020A151501757 (to GYG); General Project of Natural Science Foundation of Guangdong Province, No. 2021A1515011435 (to SY)

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摘要：

文题释义：
金丝桃苷：是一种黄酮醇苷类化合物，广泛存在于金丝桃科、蔷薇科、藤黄科、豆科、杜鹃花科和卫矛科等多种植物中，是中药菟丝子的主要成分之一。
子宫内膜损伤：女性因宫腔操作、内分泌、药物等各种因素造成子宫内膜正常的结构被破坏，导致子宫内膜损伤，内膜损伤既可表现为宫腔粘连也可表现为未见明显粘连，但内膜表现为发育不良的薄型子宫内膜。

背景：金丝桃苷具有抗炎、抗氧化等多种药理作用，但将其应用于修复子宫内膜损伤的研究并不多见。
目的：制备金丝桃苷纳米粒，利用泊洛沙姆407搭载金丝桃苷纳米粒，研究其对大鼠子宫内膜损伤的修复作用。
方法：分别制备金丝桃苷纳米粒、泊洛沙姆407水凝胶与泊洛沙姆407水凝胶搭载金丝桃苷纳米粒。取24只雌性SD大鼠，随机分4组，每组6只：模型组、单纯水凝胶组、载药水凝胶组以搔刮法建立子宫内膜损伤模型，分别向子宫内注射PBS、泊洛沙姆407水凝胶、泊洛沙姆407水凝胶搭载金丝桃苷纳米粒，空白对照组仅行开腹不进行造模。造模7 d后取材，苏木精-伊红染色观察子宫内膜形态学变化，采用ELISA法检测子宫内膜组织中白细胞介素1β、白细胞介素8、肿瘤坏死因子α水平，免疫荧光染色检测宫内膜组织中血管内皮生长因子、角蛋白、波形蛋白的表达。
结果与结论：①苏木精-伊红染色显示，与空白对照组比较，模型组大鼠子宫内膜层变薄，内膜结构不完整，血管及腺体及明显减少稀疏；与模型组比较，单纯水凝胶组大鼠子宫内膜增厚、内膜结构较完整，载药水凝胶组大鼠子宫内膜增厚、内膜结构较完整、腺体较丰富；②与空白对照组比较，模型组的白细胞介素1β、白细胞介素8、肿瘤坏死因子α水平均升高(P < 0.01)；与模型组比较，单纯水凝胶组、载药水凝胶组的白细胞介素1β、白细胞介素8、肿瘤坏死因子α水平均下降(P < 0.01)；③免疫荧光染色显示，与空白对照组比较，模型组的血管内皮生长因子、角蛋白、波形蛋白表达均降低(P < 0.01)；与模型组比较，载药水凝胶组血管内皮生长因子、角蛋白、波形蛋白表达均升高(P < 0.01)，单纯水凝胶组血管内皮生长因子表达升高(P < 0.01)；④结果表明，水凝胶搭载金丝桃苷纳米粒对大鼠子宫内膜损伤有修复作用。

https://orcid.org/0000-0001-9148-1484(李玥)

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料；口腔生物材料；纳米材料；缓释材料；材料相容性；组织工程

关键词: 金丝桃苷, 水凝胶, 泊洛沙姆407, 子宫内膜损伤, 离子交联法, 纳米粒, 组织修复

Abstract: BACKGROUND: Hyperoside has many pharmacological effects such as anti-inflammation and anti-oxidation, but there are few studies on its application in repairing endometrial injury. 
OBJECTIVE: To prepare hyperoside nanoparticles and to study the repairing effect of poloxamer 407 carrying hyperoside nanoparticles on endometrial injury in model rats. 
METHODS: Hyperoside nanoparticles, poloxamer 407 hydrogel and poloxamer 407 hydrogel with hyperoside nanoparticles were prepared separately. Twenty-four female SD rats were randomly divided into four groups (n=6): model group, blank control group, hydrogel group, and drug-loaded hydrogel group. Rat models of endometrial injury were established by scratching method in the model group, hydrogel group and drug-loaded hydrogel group. PBS, poloxamer 407 hydrogel and poloxamer 407 hydrogel with hyperoside nanoparticles were injected into the uterus of rats in the model group, hydrogel group and drug-loaded hydrogel group. The blank control group received only laparotomy without modeling. The model was taken 7 days after the injection. The morphological changes of rat endometrium were observed by hematoxylin-eosin staining. The expression of interleukin-1β, interleukin-8, and tumor necrosis factor-α in the endometrial tissue of rats in each group was detected by ELISA. Immunofluorescence staining was used to detect the expression of vascular endothelial growth factor, keratin and vimentin in endometrial tissue.
RESULTS AND CONCLUSION: (1) Hematoxylin-eosin staining showed that compared with the blank control group, the endometrial layer of the rats in the model group became thinner, the endometrial structure was incomplete, and the blood vessels and glands were significantly reduced and sparse. Compared with the model group, the endometrium of the rats in the hydrogel group was thickened and the endometrial structure was relatively complete. The endometrial structure of the rats in the drug-loaded hydrogel group was thickened, the endometrial structure was relatively complete, and the glands were more abundant. (2) Compared with the blank control group, the levels of interleukin-1β, interleukin-8, and tumor necrosis factor-α were all increased in the model group (P < 0.01). Compared with the model group, the levels of interleukin-1β, interleukin-8, tumor necrosis factor-α decreased in the hydrogel group and drug-loaded hydrogel group (P < 0.01). (3) Immunofluorescence staining showed that compared with the blank control group, the expression levels of vascular endothelial growth factor, keratin and vimentin were decreased in the model group (P < 0.01). Compared with the model group, the expression levels of vascular endothelial growth factor, keratin and vimentin were all increased in the drug-loaded hydrogel group (P < 0.01), and the expression of vascular endothelial growth factor was increased in the poloxamer 407 group (P < 0.01). (4) These results confirm that hydrogel carrying hyperoside nanoparticles has a repairing effect on the rat endometrial injury model. 

Key words: hyperoside, hydrogel, poloxamer 407, endometrial injury, ion crosslinking method, nanoparticle, tissue repair

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