泛素-蛋白酶体抑制剂MG132上调Wnt/β-catenin信号通路改善骨质疏松的实验研究  

Experimental study of proteasome inhibitor MG132 up-regulates Wnt/β-catenin signaling pathway to improve osteoporosis

作　　者：邵荣学[1] 张亮 杨贺杰[1] 张志敬[1] 乐军[1] 潘浩[1] 周辉[1] 全仁夫[2] SHAO Rong-xue;ZHANG Liang;YANG He-jie;ZHANG Zhi-jing;YUE Jun;PAN Hao;ZHOU Hui;QUAN Ren-fu(Hangzhou Hospital of Traditional Chinese Medicine,Hangzhou 310007,Zhejiang,China;不详)

机构地区：[1]杭州市中医院,浙江杭州310007 [2]浙江中医药大学附属江南医院,浙江杭州311201

出　　处：《中国骨伤》2022年第1期59-64,共6页China Journal of Orthopaedics and Traumatology

基　　金：杭州市卫生计生科技计划项目(编号:2018A60)。

摘　　要：目的:探讨泛素-蛋白酶体抑制剂MG132改善骨质疏松的机制。方法:32只雌性SD大鼠,体质量220~250 g,8周龄,分为4组(n=8)。A组和B组大鼠采用去卵巢法制备骨质疏松症模型,造模成功后分别给予蛋白酶体抑制剂MG132和二甲基亚砜(dimethyl sulfoxide,DMSO)干预;C组为假手术对照组,D组为正常组,C组及D组均给予MG132干预。分别于给药后6、12周分批处死动物,于股骨颈组织取材,行病理形态学观察,Micro-CT分析,检测组织中20S蛋白酶体活性,Wnt和β-catenin的表达。结果:形态学观察显示:A组,骨小梁轻度变细,呈网状,偶有中断;B组,骨小梁明显变细、变薄,不连续;C组与D组相似,骨小梁形态结构完整,排列呈网状。骨密度(bone mineral density,BMD),骨表面积(bone surface,BS),骨体积分数(bone volume/total volume,BV/TV)及骨小梁厚度(trabecular thickness,Tb.Th)的分析结果显示:不同时间点,B组的参数比较均差于其他各组(P<0.05),A组的BS差于C组和D组(P<0.05),C组和D组所有参数差异无统计学意义。20S蛋白酶体的RFU值检测结果显示:B组显著高于其他各组(P<0.05);Western blot检测结果显示,A组Wnt蛋白和β-catenin蛋白的灰度值显著高于其他各组(P<0.05)。结论:泛素-蛋白酶体抑制剂MG-132可抑制β-catenin蛋白的降解,从而调控Wnt/β-catenin信号通路,延缓骨质疏松的发生和发展。Objective To explore the mechanism of proteasome inhibitor MG132 in improving osteoporosis.Methods:Total of 32 female SD rats,weighing 220 to 250 g and 8 weeks old,were selected.They were randomly divided into 4 groups(n=8).Rats of group A and group B were cut off ovaris on both sides to make model of osteoporosis,and then they were given proteasome inhibitors MG132 and dimethyl sufoxide(DMSO)respectively.Group C was a sham group and rats were given MG132.Group D was a normal group and rats were given MG132 too.The rats were killed in batches at 6 and 12 weeks after administration,and the femoral neck tissues were obtained.Relevant data were analyzed,such as pathomorphological observation,micro-CT analysis,detection of 20S proteasome activity in tissues,and expression of Wnt andβ-catenin.Results:Morphological observation showed that the trabecular were slightly thinner,reticulated,and occasionally interrupted in group A,while the trabecular were obviously thinner and discontinuous in group B.And the trabecular were intact and arranged reticulated in group C and D.The analysis results of bone mineral density(BMD),bone surface(BS),bone volume/total volume(BV/TV)and trabecular thickness(Tb.Th)showed that group B was worse than other groups in all parameters at different time points(P<0.05),and group A was worse than group C and group D in BS(P<0.05),there was no significant difference in all parameters between group C and group D.RFU value of 20S proteasome in group B was significantly higher than that in other groups(P<0.05).According to the results of Western blot,the gray values of Wnt protein andβ-catenin protein in group A were significantly higher than those in other groups(P<0.05).Conclusion:MG-132,a ubiquitin proteasome inhibitor,can regulate Wnt/β-catenin signaling pathway by inhibiting the degradation ofβ-catenin protein,and delaying the occurrence and development of osteoporosis.

关 键 词：蛋白酶体抑制剂 WNT/Β-CATENIN 信号通路 骨质疏松 

分 类 号：R68[医药卫生—骨科学]