摘要
探讨了灯盏花乙素(Scu)调节Janus蛋白酪氨酸激酶2(JAK2)/信号转导与转录激活子3(STAT3)信号通路对PMOP大鼠骨密度、骨生物力学性能及骨微结构的影响.实验将大鼠分为Sham组、PMOP组、Scu-L、Scu-M、Scu-H组、Coumermycin A1组(JAK2/STAT3信号通路激活剂),除Sham组外,其余组均用双侧卵巢切除复制PMOP大鼠模型.双能X线骨密度仪、三点弯曲实验、Micro CT分别测定大鼠股骨骨密度(BMD)、生物力学状况及微结构变化;HE染色观察大鼠股骨病理损伤;ELISA法评估骨代谢指标血清碱性磷酸酶(ALP)、骨钙素(OCN)和Ⅰ型胶原交联C-末端肽(CTX-I)水平;Western blot检测股骨组织中JAK2/STAT3通路蛋白表达.实验结果显示相较于Sham组,PMOP组BMD、最大强度、最大负荷和弹性模量、BV/TV、Tb.N、Tb.Th、ALP、OCN降低,CTX-1、p-JAK2/JAK2、p-STAT3/STAT3表达升高(P＜0.05);相较于PMOP组,Scu-L、Scu-M、Scu-H组BMD、最大强度、最大负荷和弹性模量、BV/TV、Tb.N、Tb.Th、ALP、OCN 升高,CTX-I、p-JAK2/JAK2、p-STAT3/STAT3 表达降低,且呈剂量依赖性(P＜0.05);Coumermycin A1可显著减弱Scu对PMOP大鼠骨密度、骨生物力学性能、及骨微结构的改善作用(P＜0.05).以上结果表明Scu可改善PMOP大鼠骨密度、骨生物力学性能及骨微结构,发挥抗PMOP作用,其作用机制可能与抑制JAK2/STAT3信号通路有关.
Abstract
The effect of scutellarin(Scu)on bone mineral density,bone biomechanical properties and bone microstructure in PMOP rats by regulating Janus protein tyrosine kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway were investigated.Rats were separated into Sham group,PMOP group,Scu-L,Scu-M,Scu-H group,and Coumermycin A1 group(JAK2/STAT3 signaling pathway activator)in this study.Except for the Sham group,all other groups were subjected to bilateral ovariectomy to replicate the PMOP rat model.Dual energy X-ray bone density meter,three-point bending experiment,and Micro CT were applied to measure the bone density(BMD),biomechanical status,and microstructural changes of rat femur,respectively.HE staining was applied to observe pathological damage of rat femur.ELISA method was applied to evaluate the levels of serum alkaline phosphatase(ALP),osteocalcin(OCN),and type Ⅰ collagen cross-linked C-terminal peptide(CTX-I)in bone metabolism indicators.Western blot was applied to detect the expression of JAK2/STAT3 pathway proteins in femoral tissue.The experimental results showed that compared to the Sham group,the PMOP group had decreased BMD,maximum strength,maximum load and elastic modulus,BV/TV,Tb.N,Tb.Th,ALP,and OCN,and increased CTX-I,p-JAK2/JAK2,and p-STAT3/STAT3 expression(P＜0.05).Compared to the PMOP group,the Scu-L,Scu-M,and Scu-H groups had increased BMD,maximum strength,maximum load and elastic modulus,BV/TV,Tb.N,Tb.Th,ALP,and OCN,and decreased CTX-I,p-JAK2/JAK2,and p-STAT3/STAT3 expression,in a dose-dependent manner(P＜0.05).Coumermycin A1 obviously reduced the improvement effects of Scu on bone density,bone bio-mechanical properties,and bone microstructure in PMOP rats(P＜0.05).Scu can improve bone density,biomechanical properties,and microstructure in PMOP rats,exert anti PMOP effects,and its mechanism of action may be related to the inhibition of the JAK2/STAT3 signaling pathway.
基金项目
2022年度黑龙江省卫生健康委科研课题(20220404070749)
维普
万方数据