摘要
目的 探讨槲皮素调节MAPK信号通路对绝经后骨质疏松大鼠模型骨形成的影响.方法 将SPF级SD雌性大鼠分为假手术组、模型组、槲皮素低、高剂量组及补佳乐组.通过ELISA法检测大鼠血清雌激素E2水平、骨代谢标志物CBF-α1、CTX-Ⅰ、PINP、OC水平、炎性指标IL-6、TNF-α、IL-1 β水平;HE染色观察大鼠骨组织形态学变化;TRAP染色观察N.Oc/BS;显微CT扫描大鼠股骨形态,测定大鼠股骨BMD、Tb.N、Tb.Th、Tb.Sp;WB检测MAPK信号通路相关蛋白表达.结果 与假手术组相比,模型组大鼠血清E2、CBF-α1、CTX-Ⅰ、PINP、OC水平降低,IL-6、TNF-α、IL-1β水平增加,N.Oc/BS增加,BMD、Tb.N、Tb.Th降低,Tb.Sp增大(P＜0.05);与模型组相比,槲皮素低、高剂量组及补佳乐组大鼠血清E2、CBF-α1、CTX-Ⅰ、PINP、OC水平增加,IL-6、TNF-α、IL-1β水平降低,N.Oc/BS降低,BMD、Tb.N、Tb.Th增高,Tb.Sp减小(P＜0.05).假手术组骨组织形态结构正常;模型组骨皮质厚度变薄,骨小梁数量减少且断裂,排列稀疏;槲皮素低、高剂量组及补佳乐组出现新生骨小梁,数量增加,骨组织形态、结构相对完整、清晰.与假手术组相比,模型组MAPK信号通路相关蛋白水平增加(P＜0.05);与模型组相比,槲皮素低、高剂量组及补佳乐组MAPK信号通路相关蛋白水平降低(P＜0.05).结论 槲皮素能够调节绝经后骨质疏松大鼠雌激素水平,改善骨代谢异常,缓解骨微结构变化,对骨质疏松具有保护作用.可能是通过抑制MAPK信号通路相关蛋白表达、减少破骨细胞形成、减少骨吸收来实现的.
Abstract
Objective To exploring the effect of quercetin-regulated MAPK signaling pathway on bone formation in a rat model of postmenopausal osteoporosis.Methods SPF-grade SD female rats were divided into sham-operated group,model group,quercetin low and high dose group,and Tonjarol group.ELISA was used to detect serum estrogen E2 level,bone metabolism markers CBF-α1,CTX-Ⅰ,PINP,and OC level,and inflammatory indexes IL-6,TNF-α,and IL-1β level in rats.HE staining was used to observe the morphology changes of the bone tissue in rats.N.Oc/BS was observed with TRAP staining.The morphology of rat femur was observed with micro-CT scanning.BMD,Tb.N,Tb.Th,and Tb.Sp of rat femur were determined.MAPK signalling pathway related protein expressions were detected with WB.Results Compared to those in the sham-operated group,serum E2,CBF-α1,CTX-Ⅰ,PINP,and OC levels decreased,IL-6,TNF-α,and IL-1β levels increased,N.Oc/BS increased,BMD,Tb.N and Tb.Th decreased,and Tb.Sp increased in the model group(P＜0.05).Compared to those in the model group,serum E2,CBF-α1,CTX-Ⅰ,PINP,and OC levels increased,IL-6,TNF-α,and IL-1β levels decreased,N.Oc/BS decreased,BMD,Tb.N,and Tb.Th increased,and Tb.Sp decreased(P＜0.05)in the quercetin low and high dosage groups and the tonic acid group.Bone tissue morphology and structure were normal in the sham-operated group.The bone cortical thickness was thin,the number of bone trabeculae was reduced and broken,and the arrangement was sparse in the model group.The newborn bone trabeculae appeared in the quercetin low-and high-dose groups and the Tonjarol group,the number of which increased,and the morphology and structure of the bone tissue were relatively intact and clear.Compared to those in the sham-operated group,the levels of MAPK signaling pathway-related proteins increased in the model group(P＜0.05).Compared to those in the model group,the levels of MAPK signaling pathway-related proteins decreased in the quercetin low-and high-dose groups and the Tonjarol group(P＜0.05).Conclusion Quercetin regulates estrogen levels,improves bone metabolism abnormalities,alleviates bone microstructural changes,and protects against osteoporosis in postmenopausal osteoporotic rats,which may be achieved by inhibiting the expression of proteins related to the MAPK signaling pathway,by reducing osteoclast formation,and by decreasing bone resorption.
基金项目
国家自然科学基金面上项目(82274544)
江西省中医药局科技项目(2023B0280)
广州市科技计划(202206010184)
广东省教育厅普通高等学校重点领域专项(2021)(2021ZDZX2005)
NETL
NSTL
万方数据