网络药理学结合动物实验探讨二仙汤对顺铂诱导的卵巢衰老大鼠骨骼肌保护作用及其分子机制  

Network pharmacology combined with animal experiments to explore the protective effect of Erxian Tang on cisplatin-induced skeletal muscle in ovarian senescent rats and its molecular mechanism

作　　者：尤凤鸣 陈瑶 陈思 王宁 赵丕文 YOU Fengming;CHEN Yao;CHEN Si;WANG Ning;ZHAO Piwen(School of Life Sciences,Beijing University of Chinese Medicine,Beijing 102401,China)

机构地区：[1]北京中医药大学生命科学学院,102401

出　　处：《环球中医药》2025年第1期27-36,共10页Global Traditional Chinese Medicine

基　　金：国家自然科学基金(81673764)。

摘　　要：目的通过网络药理学分析和动物实验研究,预测并验证二仙汤通过雌激素受体介导磷脂酰肌醇-3-激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)/叉头框蛋白O(forkhead box O,FoxO)信号通路对顺铂诱导卵巢衰老大鼠骨骼肌的保护作用及其分子机制。方法利用网络药理学方法筛选二仙汤的有效成分及其靶点和肌肉质量下降(肌肉减少)的相关靶基因,将筛选出的关键靶点进行京都基因与基因组百科全书和基因本体论富集分析。动物实验选取40只7周龄SD雌性大鼠,随机分为空白对照组、模型对照组、阳性对照(戊酸雌二醇)组、二仙汤低剂量组、二仙汤高剂量组,每组8只。除正常对照组外,剩余各组均采取腹腔注射顺铂制备卵巢衰老模型,正常对照组与模型对照组灌胃生理盐水,二仙汤低剂量组与二仙汤高剂量组每天分别予以7.8 g/kg、15.6 g/kg灌胃,阳性对照组每天给予戊酸雌二醇0.09 mg/kg灌胃,各组持续给药28天。28天实验结束后麻醉、取材。苏木精—伊红染色法染色观察大鼠后肢骨骼肌形态学变化,并计算骨骼肌横截面面积;蛋白印迹法检测PI3K/Akt/FoxO信号通路相关蛋白表达情况。结果(1)网络药理学检测结果表明,二仙汤治疗肌少症的主要通路有雌激素信号通路、PI3K/Akt信号通路、FoxO信号通路等。(2)动物实验结果表明:与空白对照组相比,模型对照组骨骼肌肌纤维横截面积明显降低(P<0.05);与模型对照组相比较,二仙汤低剂量组骨骼肌肌纤维横截面积明显增加(P<0.05),阳性对照组和二仙汤低剂量组磷酸化FoxO3a及磷酸化Akt/Akt蛋白表达显著升高(P<0.01),二仙汤低剂量组PI3K及B淋巴细胞瘤-2蛋白表达显著升高(P<0.01)。结论二仙汤可以明显改善顺铂诱导的卵巢衰老大鼠骨骼肌肌肉质量,其作用机制与激活雌激素受体介导的PI3K/Akt/磷酸化FoxO3a信号传导通路和抗凋亡作用密切相�Objective To predict and validate the protective effect of Erxian Tang on the skeletal muscle of cisplatin-induced ovarian senescent rats through estrogen receptor-mediated phosphatidylinositol 3-kinase/protein kinase B/forkhead transcription factorsignaling pathway and its molecular mechanism through network pharmacological analyses and animal experimental studies.Methods The active ingredients of Erxian Tang and its targets and target genes related to muscle mass loss(muscle reduction)were screened using network pharmacology methods,and the screened key targets were analyzed by Kyoto encyclopedia of genes and genomes and gene ontology enrichment.For the animal experiment,407-week-old SD female rats were selected and randomly divided into the normal control group,the model control group,the positive control(estradiol)group,the Erxian Tang low-dose group and the Erxian Tang high-dose group.Except for the blank control group,all the remaining groups were injected intraperitoneally with cisplatin to prepare the ovarian aging model,and the normal control group and the model control group were gavaged with saline,the Erxian Tang low-dose group and the Erxian Tang high-dose group were gavaged with 7.8 g/kg and 15.6 g/kg per day,respectively,and the positive control group was given with estradiol valerate at 0.09 mg/kg per day,and the drugs were administered continuously for 28 days in all the groups.The dynamic changes of body weight were continuously observed,and the animals were anesthetized and sampled after 28 days.hematoxylin-eosin staining staining was used to observe the morphological changes of the skeletal muscles of the hind limbs of rats,and the cross-sectional area of skeletal muscles was calculated;The changes of the expression of the proteins related to the PI3K/Akt/FoxO signaling pathway were detected by the Western blot method.Results(1)The results of network pharmacology showed that the main pathways of Erxian Tang in the treatment of sarcopenia included estrogen signaling pathway,PI3K/Akt signaling p

关 键 词：二仙汤 雌激素 顺铂 肌肉质量下降 磷脂酰肌醇-3-激酶/蛋白激酶B/磷酸化叉头框蛋白O3a 

分 类 号：R285.5[医药卫生—中药学]