Raloxifene, a selective estrogen receptor modulator, reduces Carrageenan-induced acute inflammation in normal and ovariectomized rats
Raloxifene, a selective estrogen receptor modulator, reduces Carrageenan-induced acute inflammation in normal and ovariectomized rats
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DOI：
10.1210/en.2005-0375
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发表时间：
2005-08-01
期刊：
影响因子：
4.8
通讯作者：
Meli, R
中科院分区：
文献类型：
--
作者：
Esposito, E;Iacono, A;Meli, R
雷洛昔芬(Raloxifene，Ral)是一种选择性雌激素受体调节剂，具有组织特异性激动剂活性。这项研究的目的是检验雷公藤对角叉菜胶诱导的急性炎症是否具有雌激素样作用。成年雌性大鼠于肿胀或胸膜炎前7wk摘除卵巢(OVX)以耗尽循环雌激素。在正常大鼠(假手术)和去卵巢大鼠中检测炎症足组织中的水肿形成和选定的炎症标记物。去势大鼠分别给予1、3、10 mg/kg的乙醛或25 mg/kg的17β-雌二醇组，于术后2d开始给药，直至角叉菜胶足肿胀或胸膜炎。卵巢摘除会放大炎症，我们发现雷公藤红素和雌二醇一样，可以减轻炎症和与脚掌浮肿和胸膜炎相关的组织损伤。在治疗的大鼠中，水肿的发展和形成以及多形核髓过氧化物酶的测定和细胞计数都有所减少。雷公藤红素和雌二醇治疗可减少炎症区域的环氧合酶-2和诱导型一氧化氮合酶的表达，并抵消卵巢切除引起的对过氧化物酶体增殖物激活的受体-γ表达的抑制，将这种受体蛋白的表达恢复到假手术水平，并确定这些药物可能具有过氧酶体增殖物激活的受体依赖的抗炎作用。此外，RAL和E_2可增加细胞保护性热休克蛋白72的表达，这可能与炎症反应的缓解密切相关。此外，我们还证实了在雄性大鼠中，一次给药即可达到抗炎作用。
Raloxifene (RAL) is a selective estrogen receptor modulator presenting tissue-specific agonist activity. The aim of this study was to examine whether RAL has an estrogenic effect on carrageenan-induced acute inflammation. Adult female rats were ovariectomized (OVX) 7 wk before edema or pleurisy to deplete circulating estrogens. Edema formation and selected inflammatory markers in inflamed paw tissue were measured in intact (sham-operated) and OVX rats. Groups of OVX rats were treated with RAL ( 1, 3, or 10 mg/kg) or 17 beta-estradiol (E-2, 25 mu g/kg), and these treatments began 2 d after surgery and continued until carrageenan paw edema or pleurisy. Ovariectomy amplifies the inflammation, and we found that RAL, as well as E2, attenuates inflammation and tissue damage associated with paw edema and pleurisy. In treated rats, there is a decrease in edema development and formation, and in polymorphonuclear myeloperoxidase measurement and cell counting. RAL and E2 treatments decrease cyclooxygenase-2 and inducible nitric oxide synthase expression in inflamed areas and counteract the inhibition of peroxisome proliferators-activated receptor-gamma expression caused by ovariectomy, restoring this receptor protein expression to sham-operated levels and identifying a possible peroxisome proliferators-activated receptor-dependent antiinflammatory effect of these drugs. Moreover, RAL and E2 increase cytoprotective heat shock protein 72 expression, which seems to be closely associated with the remission of the inflammatory reaction. In addition, we confirm the antiinflammatory effect of RAL in male rats, using a single administration of RAL or E2.