Guo Ying, Zhang Chen-yan, Tian Ying, DI Jian-min, Qin Shan
Department of Obstetrics and Gynecology, Third Hospital of Hebei Medical University, Shijiazhuang 050051, China.
Zhonghua Fu Chan Ke Za Zhi. 2012 Jun;47(6):458-62.
To investigate mechanism of cyclooxygenase-2 (COX-2) in bone loss in a postmenopausal osteoporosis (PMOP) rat mode with ovarietomy (OVX).
Forty female Sprague Dawley adult rats at age of 3 months were randomly divided into 4 groups, 10 in each group, including sham-operated (sham) group, OVX group, OVX treated with nilesteriol (OVX + E) group and OVX treated with aspirin (OVX + P) group. All rats in OVX, OVX + E and OVX + P groups underwent ovarietomy under abdominal anesthesia with 10% chloral hydrate. Rats in sham group were only taken with fat tissue with same weight under bilateral ovary. After surgery, penicillin was administered to prevent infection. At day 7 after surgery, agents were given by intragastric administration for 12 weeks. Nilestriol at 1.0 mg/kg was used in OVX + E group once a week, aspirin at 45 mg×kg⁻¹(×d⁻¹ was used in OVX + P group once a day. Saline with same volume was used in rats in sham and OVX groups. All agents were administered one time per day. Dose of agents were adjusted by weight per week. At end of study, bone mineral density (BMD) of right femurs and lumbar vertebrae 3-5 (L(3-5)) were measured. Morphology of bone was detected by hematoxylineosin, and expression of COX-2 was determined by immunohistochemistry staining.
(1) BMD:BMD of right femur and L(3-5) was (0.209 ± 0.010) g/cm² and (0.230 ± 0.012) g/cm² in sham group and (0.181 ± 0.008) g/cm² and (0.201 ± 0.016) g/cm² in OVX group, which reached statistical difference (P < 0.01). BMD of right femur and L(3-5) was (0.203 ± 0.009) g/cm² and (0.224 ± 0.028) g/cm² in OVX + E group and (0.200 ± 0.011) g/cm² and (0.204 ± 0.003) g/cm² in OVX + P group, which were all higher than those in OVX group (P < 0.01, P < 0.05). However, there was no statistical difference in BMD between OVX + E and OVX + P group (P > 0.05). (2) Morphology of bone:bone trabeculae became fewer and degenerated in OVX group. However, bone trabeculae were regular and dense in OVX + P group and OVX + E group, which were similar to those in sham group. (3) Expression of COX-2:cells with COX-2 positive and expression of COX-2 around bone trabeculae in OVX group were more than those in sham, OVX + E and OVX + P group.
COX-2 plays an important role in PMOP. Aspirin could prevent bone loss by decreasing COX-2 expression in OVX rats.
通过去卵巢（OVX）建立绝经后骨质疏松症（PMOP）大鼠模型，探讨环氧合酶-2（COX-2）在骨质流失中的作用机制。
将40只3月龄雌性Sprague Dawley成年大鼠随机分为4组，每组10只，包括假手术（sham）组、OVX组、尼尔雌醇治疗的OVX组（OVX + E组）和阿司匹林治疗的OVX组（OVX + P组）。OVX组、OVX + E组和OVX + P组的所有大鼠在10%水合氯醛腹腔麻醉下进行去卵巢手术。sham组大鼠仅在双侧卵巢下取相同重量的脂肪组织。术后给予青霉素预防感染。术后第7天，通过灌胃给药12周。OVX + E组每周一次给予尼尔雌醇1.0 mg/kg，OVX + P组每天一次给予阿司匹林45 mg×kg⁻¹（×d⁻¹）。sham组和OVX组大鼠给予相同体积的生理盐水。所有药物均每天给药一次。每周根据体重调整药物剂量。研究结束时，测量右侧股骨和腰椎3-5（L(3-5)）的骨密度（BMD）。通过苏木精-伊红染色检测骨形态，并通过免疫组织化学染色测定COX-2的表达。
（1）骨密度：sham组右侧股骨和L(3-5)的骨密度分别为（0.209 ± 0.010）g/cm²和（0.230 ± 0.012）g/cm²，OVX组为（0.181 ± 0.008）g/cm²和（0.201 ± 0.016）g/cm²，差异有统计学意义（P < 0.01）。OVX + E组右侧股骨和L(3-5)的骨密度分别为（0.203 ± 0.009）g/cm²和（0.224 ± 0.028）g/cm²，OVX + P组为（0.200 ± 0.011）g/cm²和（0.204 ± 0.003）g/cm²，均高于OVX组（P < 0.01，P < 0.05）。然而，OVX + E组和OVX + P组之间的骨密度差异无统计学意义（P > 0.05）。（2）骨形态：OVX组骨小梁减少且退变。然而，OVX + P组和OVX + E组骨小梁规则且致密，与sham组相似。（3）COX-2表达：OVX组中COX-2阳性细胞及骨小梁周围COX-2的表达高于sham组、OVX + E组和OVX + P组。
COX-2在PMOP中起重要作用。阿司匹林可通过降低OVX大鼠COX-2的表达来预防骨质流失。
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