中药新药与临床药理2025，Vol.36Issue(4)：515-521,7.DOI:10.19378/j.issn.1003-9783.2025.04.004
加味芍药甘草汤对他莫昔芬诱导的子宫腺肌病小鼠血管生成相关因子的影响
Effect of Jiawei Shaoyao Gancao Decoction on Angiogenesis-Related Factors in Tamoxifen-Induced Mice with Adenomyosis
摘要
Abstract
Objective To investigate the effects of Jiawei Shaoyao Gancao Decoction(JSGD)on vascular endothelial growth factor(VEGF),hypoxia-inducible factor-1α(HIF-1α)and microvessel density(MVD)in Tamoxifen-induced adenomyosis(AM)mice.Methods A total of 36 female ICR neonatal mice were selected as the research objects.There were 6 mice randomly selected as the normal group,and the remaining 30 mice were used as the model group.After 2 days and 5 days of birth,the mice in the model group were given 2.7 µmol·kg-1 Tamoxifen+5 µL·g-1 peanut oil,lecithin and condensed milk mixture(volume ratio=2∶0.2∶3)to establish AM mice model.After the successful replication of the model in the week 16,24 mice were randomly divided into model group,JSGD high-dose group(5.972 g·kg-1·d-1),JSGD low-dose group(2.986 g·kg-1·d-1)and Dienogest group(0.362 mg·kg-1·d-1),with 6 mice in each group.They were given intragastric administration once a day for 3 consecutive weeks.The pathological changes of uterine tissue in mice were observed by HE staining and scored according to AM standard grading.Serum ALT and AST levels were detected by colorimetry,and serum VEGF levels were detected by ELISA.The mRNA expression levels of VEGF and HIF-1α in uterine tissue were detected by RT-PCR.The expression levels of VEGF and CD31 in uterine tissues were detected by immunofluorescence.Results There was no significant difference in serum ALT and AST levels in each group(P＞0.05),indicating that Tamoxifen modeling method and JSGD had no effect on ALT and AST levels in AM mice.Compared with the normal group,the score of endometrial invasion in the model group was significantly increased(P＜0.01),suggesting that the AM model mice were successfully replicated.Serum VEGF level was significantly increased(P＜0.01).The mRNA expressions of VEGF and HIF-1α in uterine tissue were significantly up-regulated(P＜0.05,P＜0.01).The expression levels of VEGF and MVD in uterine tissue were significantly increased(P＜0.01).Compared with the model group,the endometrial invasion scores of mice in the JSGD high-and low-dose groups and the Dienogest group were significantly decreased(P＜0.05);the serum VEGF level of mice in the low-dose JSGD group was significantly decreased(P＜0.05).The mRNA expression of VEGF in uterine tissue of mice in JSGD high-dose group,JSGD low-dose group and dienogest group was significantly down-regulated(P＜0.01).The expression levels of VEGF and MVD in uterine tissue were significantly decreased(P＜0.01).Conclusion JSGD can inhibit the expressions of VEGF,HIF-1α and CD31 in uterine tissue of AM mice induced by Tamoxifen,reduce the level of MVD,and play a role in the treatment of AM by regulating angiogenesis.关键词
加味芍药甘草汤/子宫腺肌病/血管生成/微血管密度/血管内皮生长因子/缺氧诱导因子1α/小鼠Key words
Jiawei Shaoyao Gancao Decoction/adenomyosis/angiogenesis/microvascular density/VEGF/HIF-1α/mice分类
医药卫生引用本文复制引用
温小慧,刘学红,黄诗雅,关永格,李坤寅..加味芍药甘草汤对他莫昔芬诱导的子宫腺肌病小鼠血管生成相关因子的影响[J].中药新药与临床药理,2025,36(4):515-521,7.基金项目
广东省普通高校重点领域专项项目(2021ZDZX2015,2023ZDZX2011) （2021ZDZX2015,2023ZDZX2011）
广州中医药大学"双一流"与高水平大学学科协同创新团队项目 （）
广州中医药大学中医学学科中医基础理论研究"揭榜挂帅"项目. （）
