Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Reprod Sci. 2011 Oct;18(10):1025-37. doi: 10.1177/1933719111404610. Epub 2011 Apr 14.
Adenomyosis is a tough disease to manage nonsurgically. Levo-tetrahydropalmatine (l-THP), a known analgesic, and andrographolide, a nuclear factor kappa B (NF-κB) inhibitor, are both active ingredients extracted from Chinese medicinal herbs. We sought to determine whether treatment of l-THP, andrographolide, and valproic acid (VPA) would suppress the myometrial infiltration, improve pain behavior, and reduce uterine contractility in a mice model of adenomyosis. Adenomyosis was induced in 55 female ICR mice neonatally dosed with tamoxifen, while another 8 (group C) were dosed with solvent only. Starting from 4 weeks after birth, hotplate test was administrated to all mice every 4 weeks. At the 16th week, all mice with induced adenomyosis were randomly divided into 6 groups, each receiving different treatment for 3 weeks: low- or high-dose l-THP, andrographolide, low-dose l-THP and andrographolide jointly, VPA, and untreated. Group C received no treatment. After treatment, the hotplate test was administered and all mice were killed. The depth of myometrial infiltration of ectopic endometrium and uterine contractility were measured and compared across groups. We found that induction of adenomyosis resulted in progressive generalized hyperalgesia, along with elevated amplitude and irregularity of uterine contractions. Treatment with either l-THP, andrographolide, VPA, or l-THP and andrographolide jointly suppressed myometrial infiltration, improved generalized hyperalgesia, and reduced the amplitude and irregularity of uterine contractions. These results suggest that increased uterine contractility, in the form of increased contractile amplitude and irregularity, may contribute to dysmenorrhea in women with adenomyosis. More importantly, l-THP, andrographolide, and VPA all seem to be promising compounds for treating adenomyosis.
子宫腺肌病的非手术治疗颇具难度。左甲四氢巴马汀（l-THP）和穿心莲内酯是从中药中提取的两种有效成分，已知具有镇痛作用，且能抑制核因子 kappa B（NF-κB）。我们旨在探究左甲四氢巴马汀、穿心莲内酯和丙戊酸（VPA）治疗是否能抑制子宫肌层浸润、改善疼痛行为、降低子宫腺肌病小鼠模型的子宫收缩力。55 只雌性 ICR 小鼠于新生期给予他莫昔芬处理以诱导子宫腺肌病，另 8 只（C 组）给予溶剂处理。自出生后第 4 周起，每 4 周对所有小鼠进行热板试验。16 周时，所有诱导出子宫腺肌病的小鼠被随机分为 6 组，每组接受不同的治疗 3 周：低或高剂量 l-THP、穿心莲内酯、低剂量 l-THP 和穿心莲内酯联合、VPA 和未治疗。C 组不进行任何治疗。治疗结束后，进行热板试验并处死所有小鼠。测量并比较各组异位子宫内膜的子宫肌层浸润深度和子宫收缩力。我们发现，诱导子宫腺肌病导致了广泛的痛觉过敏逐渐加重，同时伴有子宫收缩幅度和不规则性增加。l-THP、穿心莲内酯、VPA 或 l-THP 和穿心莲内酯联合治疗均可抑制子宫肌层浸润，改善全身性痛觉过敏，并降低子宫收缩幅度和不规则性。这些结果表明，子宫收缩力增加，表现为收缩幅度增加和不规则性增加，可能是子宫腺肌病患者痛经的原因之一。更重要的是，l-THP、穿心莲内酯和 VPA 似乎都是治疗子宫腺肌病的有前途的化合物。
