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小百科  ›  陈皮酵素可以体外遏制小鼠的肝纤维化
桂皮 pubmed 晓酵素 肝纤维化 陈皮
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Nan Fang Yi Ke Da Xue Xue Bao. 2021 Apr 20; 41(4): 588–592.
Chinese. doi: 10.12122/j.issn.1673-4254.2021.04.16
PMCID: PMC8110446
PMID: 33963720

Language: Chinese | English

陈皮酵素可体内抑制小鼠的肝纤维化

Inhibitory effect of Xinhui citrus fermentation liquor on liver fibrosis in mice

曾 兵 , 1, * 廖 柏鸿 , 1 周 东耀 , 2 白 英明 , 2 陈 恒星 , 2 陈 柏忠 , 3 and 朱 志博 1, *

曾 兵

南方医科大学中西医结合医院临床研究中心，广东 广州 510315, Clinical Research Center, TCM-Integrated Hospital of Southern Medical University, Guangzhou 510315, China

Find articles by 曾 兵

廖 柏鸿

南方医科大学中西医结合医院临床研究中心，广东 广州 510315, Clinical Research Center, TCM-Integrated Hospital of Southern Medical University, Guangzhou 510315, China

Find articles by 廖 柏鸿

周 东耀

南方医科大学中西医结合医院检验科，广东 广州 510315, Department of Clinical Laboratory, TCM-Integrated Hospital of Southern Medical University, Guangzhou 510315, China

Find articles by 周 东耀

白 英明

南方医科大学中西医结合医院检验科，广东 广州 510315, Department of Clinical Laboratory, TCM-Integrated Hospital of Southern Medical University, Guangzhou 510315, China

Find articles by 白 英明

陈 恒星

南方医科大学中西医结合医院检验科，广东 广州 510315, Department of Clinical Laboratory, TCM-Integrated Hospital of Southern Medical University, Guangzhou 510315, China

Find articles by 陈 恒星

陈 柏忠

广东新宝堂生物科技有限公司，广东 江门 529100, Guangdong Xinbaotang Biological Technology Co, Ltd., Jiangmen 529100, China

Find articles by 陈 柏忠

朱 志博

南方医科大学中西医结合医院临床研究中心，广东 广州 510315, Clinical Research Center, TCM-Integrated Hospital of Southern Medical University, Guangzhou 510315, China 南方医科大学中西医结合医院临床研究中心，广东 广州 510315, Clinical Research Center, TCM-Integrated Hospital of Southern Medical University, Guangzhou 510315, China 南方医科大学中西医结合医院检验科，广东 广州 510315, Department of Clinical Laboratory, TCM-Integrated Hospital of Southern Medical University, Guangzhou 510315, China 广东新宝堂生物科技有限公司，广东 江门 529100, Guangdong Xinbaotang Biological Technology Co, Ltd., Jiangmen 529100, China A : HE staining of the liver tissue in vehicle group, XCFL group, CCl 4 group and treatment group mice (Original magnification: ×10). B : The body weight of vehicle group, CCl 4 group and treatment group mice ( n =7). XCFL: Xinhui citrus fermentation liquor.

2.3. 陈皮酵素对小鼠肝纤维化胶原沉积的影响

结果显示，对照组和陈皮酵素组未见胶原沉积（ 图 3A ）。模型组在第1周就出现了胶原沉积，形成纤维隔膜。在接下来的几周内，纤维隔膜增多，并开始出现纤维桥连和结节。然而，给予陈皮酵素后小鼠的胶原沉积相对减少。尤其在前5周，实验组胶原沉积现象较模型组明显改善。第5周后，实验组肝纤维化程度逐渐接近持续灌胃CCl 4 的模型组，此时，肝损伤程度开始不可逆转。根据染色的组织切片中纤维隔膜、纤维桥连和结节的发展程度，对不同周的肝组织进行Ishak评分，实验组的Ishak评分低于模型组（ 图 3B ）。前5周两组评分差异有统计学意义（ P < 0.05），但后6~8周的差异无统计学意义（ P > 0.05）。

An external file that holds a picture, illustration, etc. Object name is nfykdxxb-41-4-588-3.jpg

陈皮酵素对CCl 4 小鼠模型肝纤维化的影响

Effect of XCFL on liver fibrosis in mice with CCl 4 -induced liver fibrosis. A : Sirius Red staining of the liver tissue in the vehicle group, XCFL group, CCl 4 group and treatment group mice (×10); B : Ishak fibrosis score of the vehicle group, XCFL group, CCl 4 group and treatment group mice ( n =7). * P < 0.05.

3. 讨论

目前关于肝纤维化的造模方法有很多种，其中CCl 4 诱导的肝纤维化模型是反映慢性肝纤维化的最佳模型，也是最接近人类的模型 [ 25 ] 。CCl 4 毒性可导致肝损伤和肝纤维化，肝损伤可导致血清和肝组织中ALT和AST水平升高 [ 26 ] 。本结果也显示，CCl 4 处理组小鼠血清中ALT和AST水平升高，这表明小鼠肝脏受到损伤，CCl 4 具有明显的致炎毒性。我们通过组织病理学检查、肝纤维化分级评价CCl 4 诱导肝纤维化的毒性作用，结果显示CCl 4 处理组小鼠肝组织中有炎性细胞浸润和胶原沉积现象，这表明本研究成功构建了CCl 4 诱导的小鼠肝纤维化模型。随后我们在此模型基础上探究了陈皮酵素的抗肝纤维化作用，给予陈皮酵素后肝功能指标水平降低，这显示出陈皮酵素的保肝作用。组织病理学结果显示局部炎症和胶原沉积程度减轻，尤其是前5周肝纤维化程度明显改善（ P < 0.05），但是第5周后，实验组和对照组的肝纤维化程度越来越接近，这说明陈皮酵素可减轻CCl 4 诱导的小鼠肝纤维化的程度，并且早期应用陈皮酵素可以延缓肝纤维化的发展。此外，灌胃CCl 4 的小鼠体质量明显减轻，这可能是由于肝功能受损导致食欲下降所致，给予陈皮酵素后小鼠体质量下降程度有所减轻。

研究表明果蔬类酵素具有抗肿瘤 [ 27 ] 、改善胃肠道菌群的多样性 [ 28 ] 并减少内脏器官的氧化损伤 [ 29 ] 等药理作用，但市面上这些酵素大都是由水果或蔬菜发酵而来，使用中药材发酵的产品很少。陈皮酵素由陈皮、新会柑橘和人参、菊花等中药材为原料经自然发酵和现代发酵技术相结合发酵而成，充分保留了新会柑和这些中药材中的活性成分 [ 7 ] 。此外，酵素在抗肝纤维化方面的研究也尚未见报道。因此本研究探讨陈皮酵素对CCl 4 诱导的肝纤维化小鼠的影响。目前木瓜发酵液在临床上已用作作为调节内分泌紊乱和抗氧化活性，以及改善免疫和抗炎反应的功能性食品 [ 30 ] ，本研究显示陈皮酵素也同样具有在临床上用作抗肝纤维化功能性食品的潜力。

综上所述，给予陈皮酵素的小鼠肝纤维化程度明显减轻，且早期应用陈皮酵素更有效，可以推断陈皮酵素可以抑制早期肝纤维化。但是，陈皮酵素抑制肝纤维化的具体机制还需要进一步的研究。

Biography

•

曾兵，在读硕士研究生，E-mail: moc.qq@554682377

Funding Statement

广东省基础与应用基础研究基金（2020A1515010412）

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