中国骨质疏松杂志

丹参素拮抗氧化应激所致骨质疏松并通过PI3k/Akt通路减少成骨细胞的凋亡

Tanshinol attenuates oxidative stress-induced osteoporosis and reduces apoptosis of osteoblasts via PI3/Akt signal pathway

DOI：10.3969/j.issn.1006-7108.2017.01.001

中文关键词: 丹参素骨质疏松 PI3k/Akt 细胞凋亡

英文关键词:Tanshinol Osteoporosis PI3k/Akt Apoptosis

基金项目:甘肃省卫生行业科研计划项目（GSWSKY-2014-09）

作者	单位
王秉义潘剑*	兰州大学第二医院骨科，甘肃兰州 730030

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中文摘要:

目的探讨丹参素拮抗醋酸泼尼松所致大鼠骨质疏松的作用机理。方法 60只雌性4月龄大鼠随机分为6组：正常对照组、模型组（醋酸泼尼松5 mg/kg 体重）、丹参素高中低剂量组（30 mg/kg 体重、20 mg/kg 体重、10 mg/kg 体重）和对照药白藜芦醇组（5 mg/kg 体重）。丹参素组和白藜芦醇组每日先给予模型组同样剂量的醋酸泼尼松，然后给予不同浓度药物处理。连续14w。将成骨细胞MC3T3-E1细胞随机分为A组（正常组）、B组（醋酸泼尼松组）、C组（醋酸泼尼松+丹参素干预组），D组（醋酸泼尼松+丹参素+Ly294002组）。采用双能X线骨密度检测仪检测腰椎及股骨的骨矿物密度（BMD）；采用TUNEL原位标记骨质疏松大鼠中骨组织检测细胞凋亡情况；同时采用Western-blot检测细胞凋亡相关蛋白Bax、AIF、cyto-C表达情况；免疫荧光和Western-blot检测成骨细胞MC3T3-E1中PI3/Akt信号通路相关蛋白pAkt表达情况。结果与模型组相比，不同浓度的丹参素和白藜芦醇均能升高BMD值（均P<0.05），降低骨质疏松大鼠骨细胞凋亡率（P<0.05），抑制凋亡相关蛋白Bax、AIF、cyto-C的表达（均P<0.05）。与A组相比，B组和D组成骨细胞凋亡率和凋亡相关蛋白Bax、AIF、cyto-C表达均增高（均P<0.05）；与B组相比，C组成骨细胞凋亡率和凋亡相关蛋白Bax、AIF、cyto-C表达均明显降低（均P<0.05）；免疫荧光和Western-blot检测显示C组pAkt表达量与B组相比明显增加（P<0.05），具有统计学意义。结论丹参素能够拮抗醋酸泼尼松诱导氧化应激所致骨质疏松大鼠中成骨细胞的凋亡，并且在体外是通过活化PI3k/Akt通路而减少成骨细胞的凋亡。

英文摘要:

Objective To investigate the effect of tanshinol on prednisone acetate-induced osteoporosis and its mechanism. Methods Sixty SD rats were selected and randomly divided into 6 groups: sham group, model group (prednisone acetate, 5mg/kg), tanshinol high-, medium-, and low-dose group (30, 20, 10 mg/kg), and resveratrol group (5 mgkg). The rats in tanshinol and resveratrol groups received same dose of prednisone acetate in the morning and then received drugs for 14 weeks. MC3T3-E1 cells were divided into 4 groups: group A (normal group), group B (prednisone acetate), group C (prednisone acetate + tanshinol), and group D (prednisone acetate + tanshinol + Ly294002). The bone mineral density (BMD) of the lumbar spine and femur was measured using dual energy X-ray absorptiometry (DEXA). The apoptosis of cells in the rat bone tissue in each group was observed with TUNEL assay. The expression of apoptosis-related proteins such as Bax, AIF, cyto-C in each group was detected with Western blotting. The expression of p-Akt in MC3T3-E1 cells was detected using immunfluorescence and Western blotting. Results Compared to those in the model group, BMD of the lumbar spine and femur in tanshinol high-, medium-, and low-dose group and resveratrol group increased (P<0.05), cell apoptosis decreased (P<0.05), and the expression of apoptosis-related proteins such as Bax, AIF, cyto-C decreased (P<0.05). Compared to those in group A, the apoptosis of osteoblasts and the expression of apoptosis-related proteins such as Bax, AIF, cyto-C in group B and D increased obviously (P<0.05). Compared to those in group B, the apoptosis of osteoblasts and the expression of apoptosis-related proteins such as Bax, AIF, cyto-C in C group decreased (P<0.05). The p-Akt expression in group C increased significantly comparing to that in group B detected with immunfluorescence and Western blotting (P<0.05). Conclusion Tanshinol antagonizes the apoptosis of osteoblasts in prednisone acetate-induced oxidative stress. Moreover, the effect of tanshinol in vitro is via the activation of PI3k/Akt pathway.

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