欧前胡素对恶病质模型小鼠的改善作用及机制研究

王雅娴; 杨全军; 郭澄

doi:10.6039/j.issn.1001-0408.2023.04.05

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欧前胡素对恶病质模型小鼠的改善作用及机制研究

药学研究 | 更新时间：2023-02-24

- 欧前胡素对恶病质模型小鼠的改善作用及机制研究
- Study on improvement effects and mechanism of imperatorin on cachexia model mice
- 中国药房 2023年34卷第4期页码：407-412
- 作者机构：
  
  1.上海中医药大学药学院，上海　201203
  2.上海交通大学医学院附属第六人民医院药剂科，上海　200233
- 作者简介：
  
  硕士研究生。研究方向：肿瘤恶病质。E-mail：somo_amour@163.com
  主任药师，博士生导师，教授。研究方向：肿瘤恶病质骨骼肌萎缩中药药理。E-mail：guopharm@126.com
- 基金信息：
  
  国家自然科学基金资助项目(82074063;81873042;81872494)
- DOI：10.6039/j.issn.1001-0408.2023.04.05
  中图分类号： R965
- 纸质出版日期：2023-02-28，
  
  收稿日期：2022-08-07，
  
  修回日期：2023-01-06，
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王雅娴,杨全军,郭澄.欧前胡素对恶病质模型小鼠的改善作用及机制研究 ^Δ[J].中国药房,2023,34(04):407-412.

WANG Yaxian,YANG Quanjun,GUO Cheng.Study on improvement effects and mechanism of imperatorin on cachexia model mice[J].ZHONGGUO YAOFANG,2023,34(04):407-412.
王雅娴,杨全军,郭澄.欧前胡素对恶病质模型小鼠的改善作用及机制研究 ^Δ[J].中国药房,2023,34(04):407-412. DOI： 10.6039/j.issn.1001-0408.2023.04.05.

WANG Yaxian,YANG Quanjun,GUO Cheng.Study on improvement effects and mechanism of imperatorin on cachexia model mice[J].ZHONGGUO YAOFANG,2023,34(04):407-412. DOI： 10.6039/j.issn.1001-0408.2023.04.05.

摘要

目的

探讨欧前胡素对恶病质模型小鼠的改善作用及机制。

方法

将15只雄性C57BL/6J小鼠随机分为空白对照组、模型组和欧前胡素组，每组5只。除空白对照组外，余下小鼠均于背部皮下接种小鼠肺癌LLC细胞混悬液，于接种的第7天开始每日灌胃给药，欧前胡素组按60 mg/kg灌胃欧前胡素混悬液（溶剂为0.5%羧甲基纤维素钠溶液），空白对照组和模型组给予等体积0.5%羧甲基纤维素钠溶液，连续给药13 d。给药期间，每日定时记录小鼠的摄食量和体质量，每两日测量一次肿瘤的长径和短径，计算肿瘤体积，取材当日称量各组小鼠骨骼肌质量和肿瘤质量，并计算去瘤体质量；观察小鼠骨骼肌病理学变化，计算骨骼肌纤维横截面积；检测小鼠骨骼肌中信号转导和转录因子3（STAT3）磷酸化水平（以p-STAT3/STAT3比值计），肌肉萎缩盒F蛋白（MAFbx）、肌细胞生成素（Myog）、B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）、胱天蛋白酶3（Caspase3）蛋白和mRNA表达水平。

结果

与空白对照组比较，模型组小鼠体质量和骨骼肌质量均显著降低（

＜0.05），摄食量有所下降；骨骼肌排列疏松，细胞间隙较大，骨骼肌纤维横截面积显著缩小；p-STAT3/STAT3比值和MAFbx、Bax、Caspase3蛋白表达量以及mRNA表达水平均显著升高（

＜0.05）；Myog、Bcl-2蛋白表达量以及mRNA表达水平均显著降低（

＜0.05）。与模型组比较，欧前胡素组小鼠体质量、去瘤体质量、骨骼肌质量均显著升高（

＜0.05），摄食量有所提高，同时肿瘤质量和肿瘤体积均显著降低（

＜0.05）；上述蛋白以及基因的表达均有显著改善（

＜0.05）。

结论

欧前胡素能改善小鼠肿瘤恶病质状态，其作用机制可能与调节泛素-蛋白酶体系统、抗细胞凋亡相关。

Abstract

OBJECTIVE

To investigate the improvement effects and mechanism of imperatorin on cachexia model mice.

METHODS

Fifteen male C57BL/6J mice were randomly divided into blank control group， model group and imperatorin group， with 5 mice in each group. Except for blank control group， the remaining mice were inoculated with LLC cell suspension subcutaneously on the dorsal surface， and the drug was administered by gavage daily from the 7th day of inoculation. The imperatorin group was gavaged with imperatorin suspension （0.5% sodium carboxymethylcellulose solution as solvent） at 60 mg/kg； blank control group and model group were given an equal volume of 0.5% sodium carboxymethylcellulose solution， for 13 d of continuous administration. During the administration period， food intake and body mass of mice were recorded daily and regularly， tumor long and short diameters were measured every two days， and tumor volume was calculated. The skeletal muscle mass and tumor mass of each group were weighed and the tumor-free body weight was calculated； the pathological changes of skeletal muscle were observed and the cross-sectional area of skeletal muscle fibers was calculated； the phosphorylation levels of signal transduction and activator of transcription 3 （STAT3）（measured as p-STAT3/STAT3 ratio）， muscle atrophy box F gene （MAFbx）， myostatin （Myog）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， Caspase3 protein and mRNA expression were all detected.

RESULTS

Compared with blank control group， body mass and skeletal muscle mass of model group were decreased significantly （

＜0.05）， and reduced food intake， loose arrangement of skeletal muscle， large cell space were observed； the cross-sectional area of skeletal muscle fiber was significantly reduced， while p-STAT3/STAT3 ratio， protein and mRNA expressions of MAFbx， Bax and Caspase3 were increased significantly （

＜0.05）. The protein and mRNA expressions of Myog and Bcl-2 were significantly reduced （

＜0.05）. Compared with model group， body weight， tumor-free weight and skeletal muscle weight were increased significantly in imperatorin group （

＜0.05）； food intake increased， while the expressions of tumor weight and volume were decreased significantly （

＜0.05）； the expressions of above proteins and genes were improved significantly （

＜0.05）.

CONCLUSIONS

Imperatorin can improve the tumor cachexia state， the mechanism of which may be related to the regulation of ubiquitin-proteasome pathway and anti-apoptosis.

关键词

欧前胡素肿瘤恶病质肌肉萎缩小鼠

Keywords

cancer cachexiamuscle atrophymice

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