Harmsen Marissa J, Juffermans Lynda J M, Kroon Muara O, Griffioen Arjan W, Huirne Judith A F
Department of Obstetrics and Gynaecology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.
Amsterdam Reproduction & Development Research Institute, Amsterdam, the Netherlands.
Angiogenesis. 2025 Jan 25;28(1):12. doi: 10.1007/s10456-024-09960-6.
Adenomyosis is characterized by abnormal uterine bleeding, dysmenorrhea and subfertility. Increased expression of angiogenesis markers in adenomyosis presents a treatment opportunity and was studied in an adenomyosis mouse model. Mice were administered tamoxifen (1 mg/kg) on neonatal days 2-5. At six weeks of age, mice received oral treatment with axitinib 3 mg/kg ('dose I/AX3', n = 34), axitinib 25 mg/kg ('dose II/AX25' n = 34), or with vehicle-only ('placebo', n = 34). The prevalence and severity of adenomyosis were assessed. An adenomyosis severity index was calculated by multiplying mean grade/mouse by the percentage affected surface area. Angiogenesis-related gene expression was evaluated using real-time quantitative PCR. 101 mice completed adenomyosis induction and could be analyzed. The prevalence of adenomyosis was 30/33 (90.0%) in dose I, 29/34 (85.3%) in dose II, and 30/34 (88.2%) in placebo treated mice (p = 0.78). High grade (2/3) adenomyosis was significantly less prevalent in mice treated with axitinib dose II (n = 19, 55.9%) than in the placebo group (n = 27, 79.4%, p < 0.05). The adenomyosis severity index was reduced by 48% in the axitinib-treated groups (dose I, p < 0.05). The expression of angiogenic growth factors was reduced in the dose I and II axitinib-treated groups compared to the placebo-treated group. Following these promising first results, further research should focus on commonality among different angiostatic drugs, potential side effects, as well as the method and timing of application.
子宫腺肌病的特征是异常子宫出血、痛经和生育力低下。子宫腺肌病中血管生成标志物的表达增加提供了一个治疗机会，并在子宫腺肌病小鼠模型中进行了研究。在出生后第2至5天给小鼠施用他莫昔芬（1毫克/千克）。在六周龄时，小鼠接受口服阿昔替尼治疗，剂量为3毫克/千克（“剂量I/AX3”，n = 34）、25毫克/千克（“剂量II/AX25”，n = 34）或仅接受载体（“安慰剂”，n = 34）。评估子宫腺肌病的患病率和严重程度。通过将平均等级/小鼠乘以受影响表面积的百分比来计算子宫腺肌病严重程度指数。使用实时定量PCR评估血管生成相关基因的表达。101只小鼠完成了子宫腺肌病诱导并可进行分析。剂量I组子宫腺肌病的患病率为30/33（90.0%），剂量II组为29/34（85.3%），安慰剂治疗组为30/34（88.2%）（p = 0.78）。阿昔替尼剂量II治疗的小鼠中高级别（2/3）子宫腺肌病的患病率（n = 19，55.9%）显著低于安慰剂组（n = 27，79.4%，p < 0.05）。阿昔替尼治疗组（剂量I，p < 0.05）的子宫腺肌病严重程度指数降低了48%。与安慰剂治疗组相比，阿昔替尼剂量I和II治疗组中血管生成生长因子的表达降低。在取得这些有希望的初步结果之后，进一步的研究应集中在不同血管生成抑制药物之间的共性、潜在副作用以及应用方法和时间上。
