Page 29 - 《中国药房》2023年4期

欧前胡素对恶病质模型小鼠的改善作用及机制研究
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2
王雅娴 1， 2＊ ，杨全军 ，郭 澄 （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
1， 2 #
民医院药剂科，上海 200233）

中图分类号 R965 文献标志码 A 文章编号 1001-0408（2023）04-0407-06
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（P＜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（P＜0.05）；Myog、Bcl-2蛋白表达量以及mRNA表达水平均显著降低（P＜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（P＜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（P＜0.05）；上述蛋白以及基因
的表达均有显著改善（P＜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。
关键词 欧前胡素；肿瘤恶病质；肌肉萎缩；小鼠

Study on improvement effects and mechanism of imperatorin on cachexia model mice
1， 2
WANG Yaxian ，YANG Quanjun ，GUO Cheng （1. School of Pharmacy， Shanghai University of Traditional
2
1， 2
Chinese Medicine， Shanghai 201203， China；2. Dept. of Pharmacy， Shanghai Sixth People’s Hospital Affiliated
to Shanghai Jiao Tong University School of Medicine， Shanghai 200233， China）
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 （P＜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
Δ 基金项目 国 家 自 然 科 学 基 金 资 助 项 目（No. 82074063，No.
significantly reduced， while p-STAT3/STAT3 ratio， protein
81873042，No.81872494）
and mRNA expressions of MAFbx， Bax and Caspase3 were
＊第一作者 硕士研究生。研究方向 ：肿瘤恶病质。E-mail：
somo_amour@163.com increased significantly （P＜0.05）. The protein and mRNA
# 通信作者 主任药师，博士生导师，教授。研究方向：肿瘤恶病质 expressions of Myog and Bcl-2 were significantly reduced （P＜
骨骼肌萎缩中药药理。E-mail：guopharm@126.com 0.05）. Compared with model group， body weight， tumor-free

中国药房 2023年第34卷第4期 China Pharmacy 2023 Vol. 34 No. 4 · 407 ·