| 陈一洲,叶勇健,李之斌,陈丹琦.金匮肾气丸调控β-catenin通路治疗去卵巢小鼠骨质疏松[J].浙江中西医结合杂志,2020,30(10): |
| 金匮肾气丸调控β-catenin通路治疗去卵巢小鼠骨质疏松 |
| Kidney-qi-tonifying pills Attenuate Osteoporosis via regulation of β-catenin Signaling Pathway in Ovariectomized Mice |
| 投稿时间：2020-04-06 修订日期：2020-08-19 |
| DOI： |
| 中文关键词: 金匮肾气丸 骨质疏松症 β-catenin 去卵巢小鼠 |
| 英文关键词:kidney-qi-tonifying pills osteoporosis β-catenin ovariectomized mice |
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| 摘要点击次数: 657 |
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| 中文摘要: |
| 目的：探究金匮肾气丸治疗去卵巢小鼠骨质疏松的疗效和分子机制。方法：24只10周龄雌性C57BL/6小鼠按照随机数字表法分为假手术组、模型组和金匮肾气丸组，每组8只。模型组和金匮肾气丸组小鼠摘除双侧卵巢造模，假手术组切除卵巢周围等量的脂肪组织。术后第4天开始灌胃干预，金匮肾气丸组给予金匮肾气丸溶液0.2 mL/天，模型组给予等量生理盐水。干预8周后，摘取小鼠双侧股骨进行Micro-CT、病理染色和qRT-PCR检测。结果：与假手术组比较，模型组骨密度[（0.90±0.07）mg/mm3比（1.21±0.10）mg/mm3；P<0.05]、骨体积分数[（26.31±2.90）%比（42.10±5.35）%；P<0.05]和骨小梁数目[（2.39±0.29）mm比（3.51±0.42）mm；P<0.05]均降低，骨小梁间距增加[（0.34±0.08）mm比（0.21±0.05）mm；P<0.05]，骨小梁厚度无显著变化[（0.12±0.01）mm比（0.12±0.03）mm；P>0.05]，骨小梁面积分数减少（12.89±4.36）%比（22.52±2.32）%；P<0.05]，骨髓腔内脂肪空泡面积[（13.01±4.95）%比（3.03±0.66）%；P<0.05]和直径[（32.03±5.62）μm比（23.22±1.90）μm；P<0.05]均增加。β-catenin及其下游Osterix和ALP基因表达减少[β-catenin：（0.387±0.139）比（1.036±0.337）；Osterix：（0.362±0.134）比（1.114±0.350）；ALP：（0.272±0.077）比（1.004±0.118）；P<0.05）]。经金匮肾气丸治疗后，小鼠股骨骨密度升高[（1.15±0.12）mg/mm3比（0.90±0.07）mg/mm3；P<0.05]，骨体积分数[（34.24±4.01）%比（26.31±2.90）%；P<0.05]和骨小梁数目[（2.72±0.25）mm比（2.39±0.29）mm；P<0.05]均升高，骨小梁间距减少[（0.26±0.03）mm比（0.34±0.08）mm；P<0.05]，骨小梁厚度无显著变化[（0.12±0.02）mm比（0.12±0.01）mm；P>0.05]，骨小梁面积分数增加[（20.17±4.88）%比（12.89±4.36）%；P<0.05]，髓腔内脂肪空泡面积[（6.96±3.58）%比（13.01±4.95）%；P<0.05]和直径[（25.43±3.91）μm比（32.03±5.62）μm；P<0.05]均减少。β-catenin、Osterix和ALP的mRNA表达升高[β-catenin：（0.877±0.224）比（0.387±0.139）；Osterix：（0.881±0.187）比（0.362±0.134）；ALP：（0.812±0.145）比（0.272±0.077）；P<0.05]。结论：金匮肾气丸能够有效延缓去卵巢小鼠骨量丢失，其可能是促进β-catenin及下游Osterix、ALP成骨基因表达，进而影响干细胞向成骨细胞分化。 |
| 英文摘要: |
| Objective: To investigate the effects and molecular mechanism of kidney-qi-tonifying pills on osteoporosis in ovariectomized mice. Methods: Twenty-four 10-weeks old female C57/BL6 mice were randomly divided into the sham-operation group, the model group and the kidney-qi-tonifying pills group by random number table method. Mice in the model and the kidney-qi-tonifying pills groups were received a resection of bilateral ovaries, while mice in the sham-operation group were only resected the equivalent para-ovarian adipose tissue. Since 4 days post-surgery, mice in the kidney-qi-tonifying pills group began to receive 0.2 ml/day drug lavage intervention, and mice in the model group receive normal saline in the same volume. At 8 weeks after the intervention, bilateral femurs were harvested from the experimental mice for Micro-CT analysis, pathological staining and qRT-PCR analysis. Results: Compared with the sham operation group, mice in the model group presented low bone mineral density [(0.90±0.07) mg/mm3 vs (1.21±0.10) mg/mm3; P<0.05], decreased bone volume fraction [(26.31±2.90) % vs (42.10±5.35) %; P<0.05], decreased trabecular number [(2.39±0.29) mm vs (3.51±0.42) mm; P<0.05], increased trabecular separation [(0.34±0.08) mm vs (0.21±0.05) mm; P<0.05], unchanged trabecular thickness [(0.12±0.01) mm vs (0.12±0.03) mm; P>0.05], decreased bone area fraction [(12.89±4.36) % vs (22.52±2.32) %; P<0.05], and increased lipid droplet area [(13.01±4.95) % vs (3.03±0.66) %; P<0.05] and diameter [(32.03±5.62) μm vs (23.22±1.90) μm; P<0.05] as well as decreased mRNA expression of β-catenin, Osterix and alkaline phosphatase (ALP) [β-catenin: (0.387±0.139) vs (1.036±0.337); Osterix: (0.362±0.134) vs (1.114±0.350); ALP: (0.272±0.077) vs (1.004±0.118); P<0.05]. After the treatment of kidney-qi-tonifying pills, mice showed improvement of bone mineral density [(1.15±0.12) mg/mm3 vs (0.90±0.07) mg/mm3; P<0.05], bone volume fraction [(34.24±4.01) % vs (26.31±2.90) %; P<0.05] and trabecular number [(2.72±0.25) mm vs (2.39±0.29) mm; P<0.05], decrease of trabecular separation [(0.26±0.03) mm vs (0.34±0.08) mm; P<0.05], unchanged trabecular thickness [(0.12±0.02) mm vs (0.12±0.01) mm; P>0.05], increased bone area fraction [(20.17±4.88) % vs (12.89±4.36) %; P<0.05], decreased lipid droplet area [(6.96±3.58) % vs (13.01±4.95) %; P<0.05] and diameter [(25.43±3.91) μm vs (32.03±5.62) μm; P<0.05], as well as increased mRNA levels of β-catenin, Osterix and ALP [β-catenin: (0.877±0.224) vs (0.387±0.139); Osterix: (0.881±0.187) vs (0.362±0.134); ALP: (0.812±0.145) vs (0.272±0.077); P<0.05]. Conclusion: Kidney-qi-tonifying pills could attenuate bone loss in ovariectomized mice possibly through activation of β-catenin and downstream osteogenic target gene (Osterix and ALP), which might promote osteogenic differentiation of mesenchyml stem cells. |
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