目的 探讨加味芍药甘草汤（JSGD）对他莫昔芬诱导的子宫腺肌病（AM）小鼠血管内皮生长因子（VEGF）、 缺氧诱导因子 1α（HIF-1α）及微血管密度（MVD）的影响。方法 将 36 只雌性 ICR 新生小鼠作为研究对象，随 机选取 6 只作为正常组，其余 30 只作为造模组。在出生后第 2~5 天，造模组小鼠给予 2.7 μmol·kg-1他莫西芬 +5 μL·g-1花生油、卵磷脂、炼乳混合液（体积比=2∶0.2∶3）滴喂以建立 AM 小鼠模型。第 16 周模型复制成功后， 将 24 只小鼠随机分为模型组、JSGD 高剂量组（5.972 g·kg-1 ·d-1 ）、JSGD 低剂量组（2.986 g·kg-1 ·d-1 ）及地诺孕素 组（0.362 mg·kg-1 ·d-1 ），每组 6 只，灌胃给药，每天 1 次，连续 3 周。采用 HE 染色法观察小鼠子宫组织病理 变化，并按照 AM 标准分级进行评分；比色法检测血清 ALT、AST 水平，ELISA 法检测血清 VEGF 水平； RT-PCR 法检测子宫组织中 VEGF、HIF-1α mRNA 表达水平；免疫荧光法检测子宫组织中 VEGF、CD31 的表 达水平。结果 各组小鼠的血清 ALT、AST 水平无明显差异（P＞0.05），表明他莫昔芬造模方法及 JSGD 对 AM 小鼠的 ALT、AST 水平无影响。与正常组比较，模型组小鼠子宫内膜侵入程度评分显著升高（P＜0.01），提示 AM 模型小鼠复制成功；血清 VEGF 水平显著升高（P＜0.01）；子宫组织 VEGF、HIF-1α mRNA 表达均显著上 调（P＜0.05，P＜0.01），VEGF 蛋白及 MVD 表达水平均显著升高（P＜0.01）。与模型组比较， JSGD 高、低剂 量组及地诺孕素组小鼠子宫内膜侵入程度评分均明显降低（P＜0.05）；JSGD 低剂量组小鼠的血清 VEGF 水平明 显降低（P＜0.05）；JSGD 高、低剂量组及地诺孕素组小鼠子宫组织 VEGF mRNA 表达均显著下调（P＜0.01）， VEGF 蛋白及 MVD 表达水平均显著降低（P＜0.01）。结论 JSGD 可以抑制他莫昔芬诱导的 AM 小鼠子宫组织 的 VEGF、HIF-1α 及 CD31 表达，降低 MVD 水平，通过调控血管生成发挥治疗 AM 的作用。

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 Tamoxifeninduced 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 downregulated （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.

R285.5

广东省普通高校重点领域专项项目（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。