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~(-8)mol/L和孕
激素浓度10~(-8)mol/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。
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
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.
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