【作者】 张萍；

【导师】 钟梅；

【作者基本信息】 第一军医大学 ， 妇产科学， 2001， 硕士

【摘要】 目的：了解各种常见症状在围绝经期妇女中的实际分布，验证激素替代疗法治疗绝经期骨质疏松症的有效性和合理性，研究MMP-2、TIMP-1在离体成骨细胞上的表达特点及雌激素对MMP-2、TIMP-1的影响，初步探讨MMP-2/TIMP-1在骨吸收中的作用。方法： 1．横断面研究性的抽样流行病学问卷调查和双盲随机对照临床试验。 2．采用免疫组化方法对成骨细胞中的MMP-2蛋白的表达及特点进行检测。 3．采用逆转录定量PCR检测雌、孕激素对成骨细胞分泌MMP-2、 TIMP-1mRNA的影响。结果： 1．调查的28种症状在1616名40-60岁（平均年龄为46.2岁）妇女的各年龄段及已绝经和未绝经分组中，均以骨质疏松症状的腰脊酸软的曾患率为最高（49.2％）。 2．调查发现的71名症状较重者（平均年龄50.7岁）纳入临床药物试验，与空白对照组相比，观察的19项临床症状（除大便干结和记忆力减退两项症状外）及其Kupperman评分值有显著改善，同时骨代谢指标OCN、ALP有显著改善。 3．MMP-2蛋白在成骨细胞上表达阳性，雌激素对MMP-2蛋白的表达有抑制作用。 4．成骨细胞分泌的MMP-2在雌、孕激素作用下呈剂量依赖性下降，与空白对照组相比有显著差异（P＜0.05），以雌激素浓度10^-8mol/L和孕激素浓度10^-8mol/L共同作用时下降最为显著（P＜0.01）。成骨细胞分泌的TIMP-1在雌、孕激素作用下变化不显著（P＞0.05）。结论： 1．流行病学调查结果显示，骨质疏松相关症状在围绝经期妇女中最为常见。激素替代治疗骨质疏松症从临床试验中表明其对骨形成有明显促进作用。 2．雌、孕激素可通过其对成骨细胞帆P－2抑制作用，促进骨形成，减缓竹吸收和骨基质降解。孕激素治疗骨质疏松症和雌激素同样具有重要意义。更多还原

【Abstract】 Objective: To investigate the distribution of the common symptoms among postmenopausal (PMOP) women, to certificate the validity and rationality of the treatment of Hormone Replacement Treatment (l-IRT) to PMOP, to study the expression of MMP-2 and TIMP- I protein in osteoblast of SD rats and to assess the change of MMP-2 and TIMP-1 induced by 17-bata extradio (E2), progesterone (P), and to understand the mechanism of MMP-2 and TIMP-l in bone resorption. Methods: 1. A cross-sectional epidemiological study by questionnaire and a double- blind randomized placebo-controlled trial were adopted. 2. The expression and localization of the MMP-2 in cultured osteoblasts were demonstrated immunohistochemically. 3. The expression of MMP-2 and TI1MP-ImRNA in cultured osteoblast were assayed by RT-PCR after E and P were administered respectively. Results: 1. The prevalent clinical symptom in 1616 cases of both premenopause and postmenopause women investigated, aged 40-60 years (mean 46.2), was back pains (49.2%) last year. 2. 19 patients were treated with placebo as control, Fufuchun was administered as HRT to 16 patients for 30 days. 16 of 19 observed symptoms and their Kuppennan’s values were significantly improved in HRT group than control. The Octeocalcin (OCN) and ALP in serum of HRT group increase significantly (p<O.O5) compaired with the control. 3. The expression of MMP-2 proteins was found in cultured osteoblats. Its expression could be inhibited by E2. 4. The expression of MMP-2 mRNA in cultured osteoblasts decreased with the dose- increase of and P. MMP-2 mRNA levels were decreased significantly when E2 and P was at lO4mol/L , but TIMP-l had no change. Conclusions: 1. The symptoms of osteoporosis is most common among preimenopausal women were confirmed by our epidemiological findings and treatment with HRT is effective. 2. ? and P might decrease the expression of MMP-2 in osteoblast, which could lead to increased degradation of bone matrix and bone resorption followed acceleration of bone loss, P has same important effect as E2 in the treatment of PMOP.更多还原