摘要
目的:探讨鸢尾素(Irisin)对绝经后骨质疏松(PMOP)大鼠骨代谢及Hippo/Yes相关蛋白(YAP)信号通路的影响.方法:采用双侧卵巢切除法构建 PMOP 大鼠模型,将所有实验大鼠分为对照组(Control组)、PMOP 组、鸢尾素低、中、高剂量组(Irisin-L、Irisin-M、Irisin-H 组)、鸢尾素高剂量+YAP抑制剂维替泊芬组(Irisin-H+VTPF 组);骨密度仪测定骨密度(BMD);Micro-CT 分析骨小梁的平均厚度(Tb.Th)、骨小梁面积百分比(Tb.Ar)、骨小梁数量(Tb.N)和骨小梁分离度(Tb.Sp);HE 染色观察股骨组织形态学变化;ELISA法检测大鼠血清中骨代谢标志物特异性碱性磷酸酶(BALP)、I 型前胶原氨基端前肽(PINP)、Ⅰ型胶原氨基端延长肽(PINP)、骨钙素(OC)、核结合因子-α1(CBF-α1)水平;West-ern blot法检测带pdz结合基序的转录共激活因子(TAZ)、YAP、p-YAP 蛋白表达水平.结果:与Control组比较,PMOP 组大鼠股骨组织的骨小梁结构紊乱,骨小梁厚度变薄,空骨陷窝明显,甚至发生轻微骨折,BMD、Tb.Th、Tb.Ar、Tb.N、BALP、P1NP、OC、CBF-α1、TAZ、YAP、p-YAP 表达水平显著降低,Tb.Sp显著升高(P<0.05);与PMOP 组比较,Irisin-L、Irisin-M、Irisin-H组大鼠股骨组织骨小梁结构逐渐排列有序,空骨陷窝减少,股骨组织损伤逐渐减轻,BMD、Tb.Th、Tb.Ar、Tb.N、BALP、P1NP、OC、CBF-α1、TAZ、YAP、p-YAP 表达水平依次显著升高,Tb.Sp依次显著降低(P<0.05);与Irisin-H组比较,Irisin-H +VTPF组大鼠股骨组织的骨小梁结构紊乱,空骨陷窝明显增加,股骨组织损伤加重,BMD、Tb.Th、Tb.Ar、Tb.N、BALP、P1NP、OC、CBF-α1、TAZ、YAP、p-YAP 表达水平显著降低,Tb.Sp显著升高(P<0.05).结论:鸢尾素可以通过激活Hippo-YAP 信号通路,调节绝经后骨质疏松大鼠骨代谢,防治骨质疏松.
Abstract
Objective:To investigate the effects of irisin on bone metabolism and Hippo/Yes associated protein(YAP)signaling pathway in postmenopausal osteoporosis(PMOP)rats.Methods:A PMOP rat mod-el was established using bilateral ovariectomy.All experimental rats divided into the following groups:control group,PMOP group,irisin low,medium,and high dose groups(Irisin-L,Irisin-M,Irisin-H groups),and high-dose irisin+YAP inhibitor Vitipofen group(Irisin-H+VTPF group);bone mineral density meter was ap-plied to measure bone mineral density(BMD);Micro-CT was applied to analyze the average thickness of tra-beculae(Tb.Th),percentage of trabecular area(Tb.Ar),number of trabeculae(Tb.N),and trabecular separation(Tb.SP);HE staining was applied to observe the morphological changes of femoral tissue;ELISA method was applied to detect the levels of bone metabolism biomarkers specific alkaline phosphatase(BALP),procollagen type Ⅰ N-terminal propeptide(PINP),osteocalcin(OC),and core binding factor-α1(CBF-α1)in serum;Western blot method was applied to detect the expression levels of transcriptional co-activator with PDZ-binding motif(TAZ),YAP,and p-YAP proteins.Results:Compared with the Control group,the trabecular bone structure of the femoral bone tissue in the PMOP group was disordered,the trabecular bone thickness was decreased,the bone marrow space was significantly increased,and even mild fractures oc-curred.The levels of BMD,Tb.Th,Tb.Ar,Tb.N,BALP,PINP,OC,RANKL,TAZ,YAP,and p-YAP were significantly decreased,and Tb.Sp was significantly increased(P<0.05).Compared with the PMOP group,the trabecular bone structure of the femoral bone tissue in the Irisin-L,Irisin-M,and Irisin-H groups was gradually arranged in order,the bone marrow space was reduced,and the femoral bone tissue damage was gradually alleviated.The levels of BMD,Tb.Th,Tb.Ar,Tb.N,BALP,PINP,OC,RANKL,TAZ,YAP,and p-YAP were significantly increased in order,and Tb.Sp was significantly decreased in order(P<0.05).Compared with the Irisin-H group,the trabecular bone structure of the femoral bone tissue in the Irisin-H + VTPF group was disordered,the bone marrow space was significantly increased,the femoral bone tissue damage was aggravated,and the levels of BMD,Tb.Th,Tb.Ar,Tb.N,BALP,PINP,OC,RANKL,TAZ,YAP,and p-YAP were significantly decreased,and Tb.Sp was significantly increased(P<0.05).Conclu-sion:Irisin can prevent and treat osteoporosis by regulating bone metabolism in OVX osteoporotic rats through the activation of the Hippo/YAP signaling pathway.
维普
万方数据