New insights into the efficacy of SR-16234, a selective estrogen receptor modulator, on the growth of murine endometriosis-like lesions
New insights into the efficacy of SR-16234, a selective estrogen receptor modulator, on the growth of murine endometriosis-like lesions
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关于选择性雌激素受体调节剂 SR-16234 对小鼠子宫内膜异位症样病变生长功效的新见解
DOI：
10.1111/aji.13023
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发表时间：
2018
影响因子：
3.6
通讯作者：
Harada Tasuku
中科院分区：
文献类型：
--
作者：
Khine Yin Mon;Taniguchi Fuminori;Nagira Kei;Nakamura Kazuomi;Ohbayashi Tetsuya;Osaki Mitsuhiko;Harada Tasuku
目的探讨选择性雌激素受体调节剂（SERM）SR-16234（SR）对小鼠子宫内膜异位症样病变的作用。卵巢切除、雌二醇替代的6周龄鼠子宫内膜异位症模型在4周内注射脂多糖（LPS）（含或不含SR）（1 mg/kg/d）或溶媒。处理完成后，对小鼠腹腔中出现的子宫内膜异位样病变进行计数、测量和收集。通过真实的实时RT-PCR评估病变中炎性细胞因子和雌激素受体（ER）的基因表达。免疫组织化学分析用于评估SR对细胞增殖，血管生成活性，炎症和NF-κB磷酸化的影响。ResultsTreatment with SR显着减少了每只小鼠病变的总数和大小，而不诱导子宫内膜生长。此外，SR下调LPS增强的VEGF、IL-6、Ptgs-2、Ccl-2和ER mRNA在子宫内膜异位症样病变中的表达。免疫组化结果显示，SR处理组Ki 67阳性细胞百分率降低，ERα、CD 3、F4/80、PECAM阳性细胞强度和阳性细胞率降低。SR还能降低NF-κB p65和磷酸化NF-κB p65的表达。结论SR对小鼠子宫内膜异位症样病变的发生发展具有一定的逆转作用。
ProblemTo evaluate the effects of SR‐16234 (SR), a selective estrogen receptor modulator (SERM), on murine endometriosis‐like lesions.Method of studyBALB/c mice (n = 53) were used to establish the murine endometriosis model. Ovariectomized, estradiol replaced, 6‐week‐old murine endometriosis model were injected with lipopolysaccharide (LPS) with or without SR (1 mg/kg/d) or vehicle, over a period of 4 weeks. Upon treatment completion, the endometriosis‐like lesions that developed in the abdominal cavity of mice were counted, measured, and collected. Gene expression of inflammatory cytokines and estrogen receptor (ER) in the lesions was assessed by real‐time RT‐PCR. Immunohistochemical analysis was used to evaluate the effect of SR on cell proliferation, angiogenic activity, inflammation, and NF‐κB phosphorylation.ResultsTreatment with SR significantly reduced the total number and size of lesions per mouse without inducing endometrial growth. In addition, SR downregulated LPS‐enhancedVegf, Il‐6, Ptgs‐2,andCcl‐2and ER mRNA expression in endometriosis‐like lesions. Immunohistochemical analysis demonstrated a decrease in percentage of positive cells of Ki67, and intensity and rate of positive cells of ERα, CD3, F4/80, PECAM by SR treatment. SR also decreased the expression of NF‐κB p65 and phospho‐NF‐κB p65.ConclusionSR has a regressive effect on the development of murine endometriosis‐like lesions.