中国组织工程研究

中国组织工程研究 ›› 2021, Vol. 25 ›› Issue (8): 1224-1228.doi: 10.3969/j.issn.2095-4344.3041

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

水飞蓟素对四氯化碳致小鼠肝损伤和骨代谢的影响

陈继铭，吴晓静，刘田丰，陈海聪，黄成硕   

  1. 广东医科大学附属医院骨科中心，广东省湛江市   524023
  • 收稿日期:2020-05-27 修回日期:2020-05-29 接受日期:2020-07-06 出版日期:2021-03-18 发布日期:2020-12-12
  • 通讯作者: 黄成硕，硕士，主治医师，广东医科大学附属医院骨科中心，广东省湛江市 524023
  • 作者简介:陈继铭，男，1980年生，广东省茂名市人，汉族，2008年广东医学院毕业，硕士，副主任医师，主要从事骨质疏松、创伤骨科、足踝外科疾病的诊治研究。
  • 基金资助:
    广东省医学科研基金(A2020459)；湛江市科技发展专项资金竞争性分配项目(2017A01026)

Effects of silymarin on liver injury and bone metabolism induced by carbon tetrachloride in mice

Chen Jiming, Wu Xiaojing, Liu Tianfeng, Chen Haicong, Huang Chengshuo   

  1. Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524023, Guangdong Province, China
  • Received:2020-05-27 Revised:2020-05-29 Accepted:2020-07-06 Online:2021-03-18 Published:2020-12-12
  • Contact: Huang Chengshuo, Master, Attending physician, Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524023, Guangdong Province, China
  • About author:Chen Jiming, Master, Associate chief physician, Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524023, Guangdong Province, China
  • Supported by:
    Guangdong Provincial Medical Research Fund, No. A2020459; Competitive Allocation Project of Zhanjiang Municipal Science and Technology Development Special Fund, No. 2017A01026

PDF

55

摘要：

文题释义：
水飞蓟素：是天然的黄酮木脂素类化合物，系从菊科植物水飞蓟的干燥果实中提取而得到的天然活性物质。该物质能保护肝脏细胞免受毒性物质侵害；有强力的抗氧化功能，能保护肝脏细胞免受自由基破坏；促进蛋白质的合成，加快制造新的肝脏细胞，或令已受损的肝脏细胞自行修复。另外水飞蓟素具有抗辐射、抗衰老、防治动脉硬化、延缓皮肤老化等功效。
肝性骨病：是慢性肝病者中出现的骨代谢变化，主要表现为骨质疏松症、骨量减低和骨软化症，其中骨质疏松症的发生率与肝病严重程度呈正相关。肝性骨病可继发于肝炎肝硬化、原发性胆汁性肝硬化/原发性胆汁性胆管炎、酒精性肝硬化。

背景：有研究发现，水飞蓟素可以调节多个基因，有助于构建骨骼并防止骨骼流失。在小鼠骨折愈合模型中，水飞蓟素补充剂可通过提高骨密度和血清碱性磷酸酶和骨钙素水平来改善胫骨愈合。
目的：观察水飞蓟素对四氯化碳致小鼠肝损伤和骨代谢的影响。
方法：普通级昆明种10周龄的小白鼠24只，雌雄各半，按体质量随机分成3组，模型组制备小鼠肝损伤模型：皮下注射体积分数40%的四氯化碳花生油溶液10 μL/g，首剂加倍，每隔5 d注射1次，然后给予蒸馏水10 mL/(kg•d)灌胃；水飞蓟素组：按模型组同法给予四氯化碳后给予水飞蓟素溶液50 mg/(kg•d)灌胃；对照组：皮下注射花生油10 μL/g，首剂加倍，每隔5 d注射1次，然后给予蒸馏水10 mL/(kg•d)灌胃；连续4周，每隔一周称1次体质量；于结束前一天晚上禁食12 h，麻醉小鼠后摘眼球取血，测定血清谷草转氨酶、谷丙转氨酶活性；取肝脏检测肝匀浆中丙二醛、谷胱甘肽过氧化物酶、超氧化物歧化酶水平；取右侧股骨检测骨钙含量；取右侧胫骨Micro CT检测骨组织结构参数变化。实验方案经广东医科大学动物实验伦理委员会批准(批准号为 PJ2013011)。
结果与结论：①与对照组相比，模型组小鼠谷草转氨酶和谷丙转氨酶活性明显增加(P < 0.05)、谷胱甘肽过氧化物酶活性明显降低(P < 0.05)，骨钙及胫骨骨体积分数、骨组织矿物密度、连接密度明显降低(P < 0.05)，结构模型指数和各向异性的程度明显增加(P < 0.05)，出现明显的肝损伤、骨量下降及骨微结构受到破坏；与模型组相比，水飞蓟素用药后明显降低谷丙转氨酶活性(P < 0.05)，亦能明显降低结构模型指数和各向异性的程度(P < 0.05)，使骨小梁结构及走向较为紧密一致，出现明显的网状结构，骨微观结构保持完整；②结果说明，给予四氯化碳后小鼠出现肝损伤且骨量下降及骨微结构受到破坏，水飞蓟素用药后对四氯化碳致小鼠肝损伤及骨丢失有一定的预防作用。
https://orcid.org/0000-0002-6375-7700 (陈继铭) 

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 水飞蓟素, 四氯化碳, 骨代谢, 肝损伤, 小鼠, 动物, Micro CT

Abstract: BACKGROUND: Studies have found that silymarin has a regulatory role in multiple genes, which contributes to bone remodeling and prevents bone loss. In a mouse model of fracture healing, silymarin supplementation can improve tibia healing by increasing bone mineral density and serum alkaline phosphatase and osteocalcin levels.
OBJECTIVE: To study the effect of silymarin on liver injury and bone metabolism induced by carbon tetrachloride in mice.
METHODS: Twenty-four common Kunming mice, 10 weeks old, half male and half female, were randomly divided into three groups according to body mass. In the control group, subcutaneous injection of peanut oil 10 μL/g (double first dose) was given once every 5 days, followed by intragastric administration of 10 mL/kg/d distilled water. In the model group, animal models were made by subcutaneous injection of 40% carbon tetrachloride, followed by the same treatments as described in the control group. In the silymarin group, intragastric administration of silymarin solution 50 mg/kg/d was given after modeling. Treatments in each group lasted for 4 weeks. Each mouse was weighed every other week and was fasted for 12 hours the night before the final treatment. Under anesthesia, the mouse eyeballs were taken and blood sample from each mouse was taken to determine the serum aspartate aminotransferase and alanine aminotransferase activity; the liver was taken to measure the levels of malondialdehyde, glutathione peroxidase and superoxide dismutase in the liver homogenate; the right femur was taken to measure the bone calcium content; and the right tibia was taken for Micro CT detection to detect the changes in bone structure parameters. An approval by the Animal Ethics Committee of Guangdong Medical University was obtained with an approval No. PJ2013011.
RESULTS AND CONCLUSION: Compared with the control group, the activity of aspartate aminotransferase and alanine aminotransferase in the model group was significantly increased (P < 0.05), glutathione peroxidase activity was significantly reduced (P  < 0.05), bone calcium and tibial bone volume fraction, bone mineral density, and connection density were significantly reduced (P  < 0.05), structural model index and anisotropy degree were significantly increased (P < 0.05), and significant liver damage and decreased bone mass and bone microstructure damage were observed. Compared with the model group, silymarin significantly reduced the activity of alanine aminotransferase (P  < 0.05), and also significantly reduced the structural model index and the degree of anisotropy (P < 0.05), making the trabecular bone structure and trend more consistent. There was a clear network structure, and the bone microstructure remained intact. After the administration of carbon tetrachloride, the mice suffered liver damage with decreased bone mass and damaged bone microstructure, and silymarin administration had a certain preventive effect on liver damage and bone loss caused by carbon tetrachloride in mice.

Key words: silymarin, carbon tetrachloride, bone metabolism, liver injury, mouse, animal, Micro CT

中图分类号: