Liu Xishi, Guo Sun-Wei
Shanghai Obstetrics and Gynecology Hospital, Shanghai College of Medicine, Fudan University, Shanghai, China.
J Obstet Gynaecol Res. 2011 Jul;37(7):696-708. doi: 10.1111/j.1447-0756.2011.01655.x. Epub 2011 Jun 9.
Emerging evidence suggests that adenomyosis, like endometriosis, may also be an epigenetic disease. In this study, we evaluated the effect of valproic acid (VPA) in ICR mice with adenomyosis, induced by neonatal dosing with tamoxifen. For all mice, we evaluated the bodyweight and the response to thermal stimuli by hotplate and tail-flick tests 4, 8, and 12 weeks after dosing, respectively, and then treated mice with low- and high-dose of VPA, progesterone (P4), P4 + VPA, or vehicle only. Three weeks after treatment, both bodyweight and thermal response tests were evaluated again before sacrifice, and the depth of myometrial infiltration was evaluated. We found that: (i) the induction of adenomyosis resulted in progressive generalized hyperalgesia as measured by hotplate and tail-flick tests, along with decreased bodyweight; (ii) treatment with VPA, P4, or a combination was efficacious in improving generalized hyperalgesia; and (iii) drug treatment appeared to reduce the myometrial infiltration, but the difference did not reach statistical significance. Thus, VPA seems to be a promising therapeutics for treating adenomyosis, as reported recently in some case series in humans.
新出现的证据表明，子宫腺肌病与子宫内膜异位症一样，可能也是一种表观遗传疾病。在本研究中，我们评估了丙戊酸（VPA）对新生期给予他莫昔芬诱导的子宫腺肌病ICR小鼠的影响。对于所有小鼠，我们分别在给药后4周、8周和12周评估体重以及通过热板试验和甩尾试验对热刺激的反应，然后用低剂量和高剂量的VPA、孕酮（P4）、P4 + VPA或仅用赋形剂处理小鼠。治疗三周后，在处死前再次评估体重和热反应试验，并评估子宫肌层浸润深度。我们发现：（i）通过热板试验和甩尾试验测量，子宫腺肌病的诱导导致进行性全身性痛觉过敏，同时体重下降；（ii）用VPA、P4或联合用药治疗可有效改善全身性痛觉过敏；（iii）药物治疗似乎可减少子宫肌层浸润，但差异未达到统计学意义。因此，正如最近在一些人类病例系列中所报道的，VPA似乎是一种有前景的治疗子宫腺肌病的药物。
