首页|基于VDR/GPX4通路探讨小檗碱对去卵巢小鼠骨丢失的抑制作用

基于VDR/GPX4通路探讨小檗碱对去卵巢小鼠骨丢失的抑制作用

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目的:探讨小檗碱对去卵巢小鼠骨丢失的影响及其可能的作用机制.方法:40只小鼠随机分为4组:假手术组、去卵巢组(模型组)、去卵巢+小檗碱组(50 mg/kg)(小檗碱组)、去卵巢+雌二醇组(100μg/kg)(雌二醇组);每组10只.分组给药12周,Western blot检测骨吸收相关因子RANKL(核因子κB受体活化因子配体)、c-Fos(细胞癌基因Fos)的蛋白表达,RT-PCR检测TRAP(抗酒石酸酸性磷酸酶)、cathepsin K(组织蛋白酶K)、MMP9(基质金属蛋白酶9)的基因表达,以及对VDR/GPX4(维生素D受体/谷胱甘肽过氧化物酶4)通路的调控作用,ELISA试剂盒检测各组骨组织MDA水平.结果:与假手术组比较,模型组骨组织RANKL、c-Fos蛋白表达和TRAP、cathepsin K、MMP9 mRNA表达水平及MDA水平均显著升高(P<0.01),VDR、GPX4蛋白表达显著下调(P<0.01),且GPX4 mRNA水平显著降低(P<0.01).与模型组比较,小檗碱组和雌二醇组骨组织RANKL、c-Fos 蛋白表达和 TRAP、cathepsin K、MMP9 mRNA表达水平及MDA水平均显著降低(P<0.01),VDR、GPX4蛋白表达显著升高(P<0.01),且GPX4 mRNA水平上调(P<0.01).结论:小檗碱可以通过激活VDR/GPX4通路,减少去卵巢小鼠骨丢失.
Inhibition Effects of Berberine on Bone Loss in Ovariectomized Mice through VDR/GPX4 Pathway
Objective:To study the inhibition effect of Berberine on bone loss in ovariectomized(OVX)mice and its possible mechanism.Methods:40 mice were randomly divided into four groups:sham group,OVX group(model group),OVX+Berberine group(50 mg/kg)(Berberine group),OVX+β-estradiol group(100μg/kg)(E2 group).Each group was given the corresponding medicine for 12 weeks.Western blot was used to detect the protein expressions of bone resorption related factors RANKL and c-Fos.RT-PCR was used to detect the gene expressions of TRAP,cathepsin K and MMP-9,and the regulation of VDR/GPX4 pathway.ELISA was used to detect the MDA level of bone tissue in each group.Results:Compared with the sham group,the expressions of RANKL,c-Fos protein and TRAP,cathepsin K,MMP-9 mRNA,MDA level in the model group were significantly increased(P<0.01),expressions of VDR,GPX4 protein were decreased(P<0.01),and GPX4 mRNA level was decreased(P<0.01).Compared with model group,the the expressions of RANKL,c-Fos protein and TRAP,cathepsin K,MMP-9 mRNA,MDA level in Berberine group and E2 group were significantly decreased(P<0.01),while the expressions of VDR,GPX4 protein were increased(P<0.01),and the mRNA level of GPX4 was up-regulated(P<0.01).Conclusion:Berberine can reduce bone loss in ovariectomized mice by activating VDR/GPX4 pathway.

osteoporosisBerberine[3-estradiolbone resorptionVDR/GPX4 pathwayovariectomized mouse

毛佳乐、林炳锋、张晓芹、雷后兴、刘爽、梅明荣、王娜妮

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浙江中医药大学附属丽水中医院·浙江 丽水 323000

浙江中医药大学药学院·浙江 杭州 310053

浙江省畲医药传承创新和开发应用中医药重点实验室·浙江丽水 323000

丽水市畲医药传承创新和开发应用中医药重点实验室·浙江 丽水 323000

浙江省中医药研究院中药研究中心·浙江 杭州 310005

浙江省民族医院·浙江 景宁 323500

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骨质疏松 小檗碱 雌二醇 骨吸收 VDR/GPX4通路 去卵巢小鼠

2024

中国中医药科技
中华中医药学会

中国中医药科技

影响因子:1.156
ISSN:1005-7072
年,卷(期):2024.31(6)