| 摘要: |
| 目的 研究氯化锂（LiCl）激活的Wnt/β-catenin信号通路对糖皮质激素引发的小鼠骨丢失的防护作用。方法 将C57BL6/J小鼠随机分为3组：对照组、骨质疏松模型组和LiCl组。骨质疏松模型组及LiCl组小鼠皮下注射地塞米松（50 mg/kg），对照组小鼠皮下注射同等剂量生理盐水。LiCl组小鼠在注射地塞米松同时通过饮用水给予LiCl（200 mg/kg）。处理5周后处死小鼠做骨组织切片，用免疫组化染色检测活性β-catenin蛋白的表达，鉴定体内Wnt/β-catenin通路激活情况；用H-E染色鉴定骨组织形态。同时取小鼠股骨进行microCT扫描，测定骨形态计量学参数。用钙黄绿素荧光标记实验鉴定新骨形成能力，抗酒石酸酸性磷酸酶（TRAP）染色鉴定骨吸收情况。结果 LiCl组小鼠体内活性β-catenin蛋白水平高于骨质疏松模型组，其骨量、骨小梁数量、骨小梁间隙及骨密度均得到改善（P<0.05），但与对照组相比差异仍有统计学意义（P<0.05）。钙黄绿素荧光标记实验证实LiCl组小鼠新骨形成能力比骨质疏松模型组有所提高，但仍低于对照组。TRAP染色证实各组小鼠骨吸收活性未发生明显改变。结论 口服LiCl能有效激活体内Wnt/β-catenin信号通路，促进新骨形成，对糖皮质激素引发的骨丢失有一定的防护作用。 |
| 关键词: Wnt/β-catenin信号通路 氯化锂 糖皮质激素类 骨质疏松 新骨形成 |
| DOI：10.16781/j.0258-879x.2017.02.0201 |
| 投稿时间：2016-08-16修订日期：2016-12-22 |
| 基金项目:国家自然科学基金（81401844），贵州省科技厅、遵义市科技局、遵义医学院联合基金[黔科合LH字（2015）7553号]，遵义医学院博士启动基金. |
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| Protective effect of LiCl-activated Wnt/β-catenin signaling pathway on glucocorticoid-induced osteoporosis |
| LIU Xing-yu,WANG Qian-xing,LU Jian,LIU Nan-jun,TANG Xian-chun,LI Jiao* |
(Department of Cell Biology, Zunyi Medical College, Zunyi 563000, Guizhou, China
*Corresponding author) |
| Abstract: |
| Objective To investigate the protective effect of lithium chloride (LiCl)-activated Wnt/beta-catenin signaling pathway on glucocorticoid-induced bone loss. Methods C57BL6/J mice were randomly divided into 3 groups,osteoporosis (OP) group and LiCl group were injected intraperitoneally once daily with dexamethasone (50 mg/kg), while control group was injected with normal saline. LiCl group was given LiCl (200 mg/kg) through water administration. After 5 weeks of treatment, mice were sacrificed within 24 h. Anti-active beta-catenin antibody was used in immunohistochemical staining to detect the activity of Wnt/beta-catenin signaling pathway. Bone morphology was observed by HE staining. Meanwhile, bone histomorphometrical parameters were analyzed by microCT. Bone formation and bone resorption of different groups were detected by calcein labeling and TRAP staining, respectively. Results The protein level of active beta-catenin was higher in LiCl group compared with OP group. Bone histomorphometrical parameters including the trabecular bone volume as a percentage of total volume (BV/TV), bone mineral density (BMD), trabecular number (Tb. N) and trabecular space (Tb.Sp) were all significantly improved in LiCl group, even though obvious difference existed between LiCl group and control group (P<0.05). Calcein labeling showed that new bone formation was markedly improved in LiCl group, but was still lower than that in control group. Bone resorption was not significantly changed among three groups as indicated by TRAP staining. Conclusion LiCl administration effectively activates Wnt/β-catenin signaling pathway in vivo, which improve new bone formation and rescue glucocorticoid-induced bone loss. |
| Key words: Wnt/β-catenin signaling pathway lithium chloride glucocorticoids osteoporosis new bone formation |
