中国骨质疏松杂志

槲皮素调控MAPK通路对绝经后骨质疏松大鼠骨形成的影响

Effect of quercetin on bone formation in postmenopausal osteoporotic rats by modulating the MAPK signaling pathway

DOI：10.3969/j.issn.1006-7108.2024.05.001

英文关键词:quercetin MAPK signaling pathway postmenopausal osteoporosis bone formation

基金项目:国家自然科学基金面上项目 (82274544)；江西省中医药管理局科技计划项目（2023B0280）；广州市科技计划项目（202206010184）；2021 年广东省教育厅普通高校重点领域专项 (2021ZDZX2005)

作者	单位
康庐琛1 魏秋实2 李文斌1 兰浩1 宁静1*	1九江市第一人民医院总院内分泌内科，江西九江 332005 2广州中医药大学第三附属医院中医骨关节科，广东广州 510378

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中文摘要:

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-1β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。

英文摘要:

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.

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