期刊
REPRODUCTIVE SCIENCES
卷 19, 期 4, 页码 360-373出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/1933719111424453
关键词
endometriosis; histone deacetylase inhibitor; hot plate test; tail-flick test; hyperalgesia; inflammation; progestin
资金
- National Science Foundation of China [30872759, 30870835, 30821002]
- National Basic Research Program [2007CB512303, 2007CB512502]
- Shanghai Science and Technology Commission [09PJD015, 10410700200]
- State Key Laboratory of Medical Neurobiology of Fudan University [09-11]
- Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases
- Ministry of Health, People's Republic of China
Accumulating evidence suggests that endometriosis is an epigenetic disease. This study was designed to evaluate the effect of valproic acid (VPA) and progesterone (P4) in a rat model of endometriosis on serum tumor necrosis factor-alpha (TNF-alpha) levels, hot plate and tail-flick latencies, lesion size, and body weight. We used 77 adult female rats, and endometriosis was induced by autotransplanting pieces of uterus (ENDO) or fat (SHAM) to the pelvic cavity. The BLANK group received no surgery. After 2 weeks, the ENDO group was further divided, randomly, into 5 groups, receiving, respectively, treatment with low- and high-dose VPA, P4 alone, VPA + P4, and no treatment. The SHAM rats received no treatment. The BLANK rats were further divided into 2 groups, one received VPA treatment and the other, no treatment. After 4 weeks, all rats were sacrificed. Response latency in hot plate and tail-flick tests, body weight, and serum TNF-alpha levels were measured before the surgery, before and after the treatment, along with lesion size. We found that induced endometriosis reduced response latency. ENDO rats receiving VPA and/or P4 treatment had significantly reduced lesion size as compared with untreated ones, and had significantly improved response to noxious thermal stimuli. They also had significantly increased weight gain. Serum TNF-alpha levels increased following surgery but eventually decreased regardless of treatment or not. In conclusion, VPA is well tolerated. Treatment with VPA significantly reduces lesion growth and improves sensitivity to nocifensive stimuli. The improvement is specific to endometriosis-induced hyperalgesia. Thus, histone deacetylase inhibitors may be a promising therapeutics for treating endometriosis.
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