机构地区:[1]Clinical Laboratory, Qilu Hospital, Shandong University, Ji-nan 250012, China [2]Department of Cardiology, Ji-nan Central Hospital Affiliated to Shandong University, Ji-nan 250012, China [3]Department of Internal Medicine, the Second Affiliated Hospital, Shandong University, Ji-nan 250012, China [4]Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry Of Health, and Department of Cardiology, Qilu Hospital, Shandong University, Ji-nan 250012, China
出 处:《Acta Pharmacologica Sinica》2011年第8期1031-1037,共7页中国药理学报(英文版)
基 金:Acknowledgements This work was supported by Grant from the Natural Science Foundation of Shandong Province, Ji-nan, Shandong, China (#Y2005C50), Grant-in-Aid for China-Japan Sasagawa Researchers, from the Ministry of Health, Beijing, China (#083). The authors are grateful to Chun-xi LIU and Zhi YANG for their excellent technical contributions.
摘 要:Aim: To assess a novel hormone replacement therapy (HRT) paradigm using raloxifene, aspirin combined with estrogen in rabbit model of menopause. Methods: Female New Zealand white rabbits were ovariectomized or sham-operated. The ovariectomized rabbits were divided into 7 groups: estradiol valerate (E2), raloxifene, aspirin, E2/raloxifene, E2/aspirin, E2/raloxifene/aspirin and vehicle. Two weeks after the operation, the rabbits were administered the above drugs for 12 weeks. Then, the mammary glands were examined histologically, uterus was weighted, and blood sample was collected for analyzing the levels of estrogen, serum lipids and monocyte chemoattractant protein (MCP)-1, and platelet aggregation. The aortic tissue was examined morphometrically. Results: Compared with E2 0.1 mg·kg^1·d^-1 treatment alone, the pairing of raloxifene 10 mg·kg^1·d^-1 with E2 significantly decreased the extent of mammary gland branches and ducts (5.53%±1.23% vs 15.4%±2.17%, P〈0.01), as well as the uterine weight (2.16±0.35 g vs 4.91±0.75 g, P〈0.01). However, E2/raloxifene or E2 alone treatment significantly stimulated platelet aggregation relative to vehicle group. Addition of aspirin 5 mg·kg^1·d^-1 reduced platelet aggregation to almost the same level as the vehicle group. E2 treatment exerted a positive effect on serum lipids and MCP-1, and a regression in aortic intimal plaque size compared to the vehicle. Raloxifene rein- forced the positive effects of E2. Conclusion'. The combination of raloxifene, aspirin and E2 exhibits positive lipid, MCP-1 and atherosclerotic responses with minimal stimulation of breast and uterine tissues as well as platelet aggregation in a rabbit model of the menopause.Aim: To assess a novel hormone replacement therapy (HRT) paradigm using raloxifene, aspirin combined with estrogen in rabbit model of menopause. Methods: Female New Zealand white rabbits were ovariectomized or sham-operated. The ovariectomized rabbits were divided into 7 groups: estradiol valerate (E2), raloxifene, aspirin, E2/raloxifene, E2/aspirin, E2/raloxifene/aspirin and vehicle. Two weeks after the operation, the rabbits were administered the above drugs for 12 weeks. Then, the mammary glands were examined histologically, uterus was weighted, and blood sample was collected for analyzing the levels of estrogen, serum lipids and monocyte chemoattractant protein (MCP)-1, and platelet aggregation. The aortic tissue was examined morphometrically. Results: Compared with E2 0.1 mg·kg^1·d^-1 treatment alone, the pairing of raloxifene 10 mg·kg^1·d^-1 with E2 significantly decreased the extent of mammary gland branches and ducts (5.53%±1.23% vs 15.4%±2.17%, P〈0.01), as well as the uterine weight (2.16±0.35 g vs 4.91±0.75 g, P〈0.01). However, E2/raloxifene or E2 alone treatment significantly stimulated platelet aggregation relative to vehicle group. Addition of aspirin 5 mg·kg^1·d^-1 reduced platelet aggregation to almost the same level as the vehicle group. E2 treatment exerted a positive effect on serum lipids and MCP-1, and a regression in aortic intimal plaque size compared to the vehicle. Raloxifene rein- forced the positive effects of E2. Conclusion'. The combination of raloxifene, aspirin and E2 exhibits positive lipid, MCP-1 and atherosclerotic responses with minimal stimulation of breast and uterine tissues as well as platelet aggregation in a rabbit model of the menopause.
关 键 词:ESTROGEN RALOXIFENE ASPIRIN ATHEROSCLEROSIS hormone replacement therapy
分 类 号:Q579.13[生物学—生物化学] TQ460.72[医药卫生—药物分析学]
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