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  

Inhibition Effects of Berberine on Bone Loss in Ovariectomized Mice through VDR/GPX4 Pathway

作　　者：毛佳乐 林炳锋 张晓芹 雷后兴 刘爽 梅明荣 王娜妮 MAO Jiale;LIN Bingfeng;ZHANG Xiaoqin;LEI Houxing;LIU Shuang;MEI Mingrong;WANG Nani(Lishui TCM Hospital Affiliated to Zhejiang Chinese Medical University,Lishui,Zhejiang 323000;School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou,Zhejiang 310053;Zhejiang Provincial Key Laboratory of She Medicine Inheritance,Innovation,Development and Application of Chinese Medicine,Lishui,Zhejiang 323000;Lishui She Medicine Inheritance,Innovation,Development and Application Key Laboratory of Chinese Medicine,Lishui,Zhejiang 323000;Zhejiang Academy of Chinese Medicine,Hangzhou,Zhejiang 310005;Zhejiang Provincial Ethnic Hospital,Jingning,Zhejiang 323500)

机构地区：[1]浙江中医药大学附属丽水中医院,浙江丽水323000 [2]浙江中医药大学药学院,浙江杭州310053 [3]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 [4]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 [5]浙江省中医药研究院中药研究中心,浙江杭州310005 [6]浙江省民族医院,浙江景宁323500

出　　处：《中国中医药科技》2024年第6期983-988,共6页Chinese Journal of Traditional Medical Science and Technology

基　　金：浙江省丽水市科技计划项目(2021GYX18)。

摘　　要：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。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)(E 2 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 E 2 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.

关 键 词：骨质疏松 小檗碱 雌二醇 骨吸收 VDR/GPX4通路 去卵巢小鼠 

分 类 号：R285.5[医药卫生—中药学]