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雷公藤甲素对去势小鼠骨质疏松模型破骨细胞分化的影响
Effect of triptolide on osteoclast differentiation in castrated mice with osteoporosis
  
DOI:10.3969/j.issn.1672-5972.2023.01.001
中文关键词:  雷公藤甲素  去势小鼠骨质疏松模型  破骨细胞
英文关键词:Triptolide  Castrated mice osteoporosis model  Osteoclast
基金项目:湖北省卫生健康委员会科研项目(WJ2021M182);湖北省中医院院级课题(20191011,20190619,2021YJKT-8,20200423-1)
作者单位邮编
胡昊 湖北省中医院骨伤诊疗中心脊柱外科湖北 武汉430074 430074
余田甜 湖北中医药大学临床学院湖北 武汉430061 430061
丰瑞兵 湖北省中医院骨伤诊疗中心脊柱外科湖北 武汉430074 430074
李朝文 武汉体育学院健康科学学院湖北 武汉430079 430079
吴刚 湖北省中医院骨伤诊疗中心脊柱外科湖北 武汉430074 430074
黄勇 湖北省中医院骨伤诊疗中心脊柱外科湖北 武汉430074 430074
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中文摘要:
      目的 探究雷公藤甲素(TP)对去势小鼠骨质疏松模型破骨细胞分化的影响,并探讨其可能的分子机制。方法 建立去势小鼠骨质疏松模型,分为假手术组(Sham组)、卵巢切除去势组(OVX组)、雷公藤甲素组(TP组)、利维爱组(Livial组),造模后第3天给予对应药物处理。治疗6周后,采用TRAP染色检测左侧股骨干骺端的破骨细胞数量。Micro-CT重建三维骨结构图像,检测左侧胫骨干骺端的骨密度(BMD)、骨小梁数目(Tb.N)、骨体积分数(BV/TV)、骨表面积组织体积比(BS/TV)、骨小梁分离度(Tb.Sp),ELISA检测外周血中IL-6、TNF-α、骨形成标志物骨钙素(OC)、骨吸收标志物抗酒石酸酸性磷酸酶(TRAcp5b)含量。Western Blot检测右侧股骨组织中p65、p-p65、IκBα、p-IκBα蛋白表达水平。结果 骨小梁周围破骨细胞数量比较:OVX组与Sham组相比明显增加;TP组与OVX组相比明显减少;TP组与Livial组比较,差异无统计学意义。骨参数分析:OVX组与Sham组相比,小鼠骨组织的BMD、Tb.N、BV/TV、BS/TV均显著下降,而Tb.Sp显著升高(P<0.01);与OVX组相比,TP组和Livial组骨组织的BMD、Tb.N、BV/TV、BS/TV均显著升高,而Tb.Sp显著下降(P<0.01);TP组与Livial组比较,差异无统计学意义(P>0.05)。IL-6、TNF-α、OC、TRAcp5b含量比较:OVX组的IL-6、TNF-α含量显著高于Sham组(P<0.01);各组间OC水平比较,差异无统计学意义(P>0.05);OVX组的TRAcp5b水平显著高于Sham组(P<0.01)。蛋白表达水平:与Sham组相比,OVX组的p65、IκBα表达水平不变,而p-p65和p-IκBα表达水平显著升高(P<0.01);TP处理后,p65、IκBα表达水平不变,而p-p65和p-IκBα表达水平却显著降低(P<0.01);TP组与Livial组比较,两者间p65、IκBα、p-p65和p-IκBα表达水平差异无统计学意义(P>0.05)。结论 TP抑制破骨细胞分化,改善了去势小鼠的骨量丢失,其分子机制可能与抑制炎症因子IL-6、TNF-α的表达及NF-κB信号通路的磷酸化水平有关。
英文摘要:
      Objective To investigate the effect of triptolide(TP) on osteoclast differentiation in emasculated mice with osteoporosis and its possible molecular mechanism.Methods To establish osteoporosis model of ovariectomized mice, they were divided into Sham group, OVX group, TP group and Livial group. The corresponding drug treatment was given on the 3rd day after modeling. Six weeks after treatment, TRAP staining was used to detect the number of osteoclasts in the left femoral metaphysis. Three dimensional images of bone structure were reconstructed by Micro-CT to detect the bone mineral density (BMD), trabecular number (Tb.N), bone volume fraction (BV/TV), bone surface area tissue volume ratio (BS/TV), trabecular separation (Tb.Sp). ELISA was used to detect the content of IL-6, TNF-α, bone formation marker osteocalcin (OC), bone resorption marker tartrate resistant acid phosphatase(TRAcp5b) in peripheral blood. Western Blot (WB) was used to detect the protein expression content of p65, p-p65, IκBα, p-IκBα.Results The number of osteoclasts around the trabecular bone: Compared with the Sham group, number in the OVX group significantly increased; number in the TP group significantly decreased compared with the OVX group; while there was no significant difference between TP group and Livial group. Analysis of bone parameter: Compared with Sham group, BMD, Tb.N, BV/TV and BS/TV in OVX group significantly decreased (P<0.01), while Tb.Sp significantly increased (P<0.01); compared with OVX group, BMD, Tb.N, BV/TV and BS/TV in TP and Livial groups significantly increased (P<0.01), while Tb.Sp significantly decreased (P<0.01); there was no significant difference between TP group and Livial group in those bone parameter. The content of IL-6, TNF-α, OC, TRAcp5b: The serum levels of inflammatory factors IL-6 and TNF-α in OVX group were significantly higher than those in Sham group (P<0.01), and the level of bone resorption marker TRAcp5b increased (P<0.01), while that in the TP group was significantly lower than that in the OVX group (P<0.01). The level of bone formation marker OC was not significantly different from Sham group. The protein expression: Compared with Sham group, the expression levels of p65 and IκBα in OVX group were unchanged, while the expression levels of p-p65 and p-IκBα significantly increased (P<0.01); after TP treatment, the expression levels of p65 and IκBα remained unchanged, but the expression levels of p-p65 and p-IκBα significantly decreased (P<0.01); there was no significant difference between TP group and Livial group in the expression levels of p65, IκBα, p-p65 and p-IκBα (P>0.05).Conclusion TP inhibits osteoclast differentiation and improves bone loss in emasculated mice. The molecular mechanism may be related to inhibiting the expression of inflammatory factors IL-6 and TNF-α and the phosphorylation level of NF-κB signaling pathway.
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