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长期电针刺激通过多种信号通路预防去卵巢骨质疏松大鼠的骨质疏松症。

Long-term electroacupuncture stimulation prevents osteoporosis in ovariectomised osteopaenic rats through multiple signalling pathways.

机构信息

Acupuncture College, Fujian University of Traditional Chinese Medicine, Fuzhou, China.

Chinese Medicine Hospital of Fuzhou, Fujian Universityof Traditional Chinese Medicine, Fuzhou, China.

出版信息

Acupunct Med. 2018 Jun;36(3):176-182. doi: 10.1136/acupmed-2016-011268. Epub 2018 Apr 6.

DOI:10.1136/acupmed-2016-011268
PMID:29625972
Abstract

BACKGROUND

The pathogenic mechanisms of postmenopausal osteoporosis (PMOP) development are complex and are related to multiple cellular signalling transduction pathways. The aim of this study was to compare the effects of electroacupuncture (EA) at GV4/GV6 versus BL20/BL23 on the bones in ovariectomised (OVX) rats to explore the pathways that mediate the effects of EA on bone.

METHODS

Forty female Sprague-Dawley rats were allocated to one of four groups (n=10 rats each) that received sham surgery (Sham group), OVX surgery only (OVX group), OVX surgery plus EA at GV4/GV6 (GV group) and OVX surgery plus EA at BL20/BL23 (BL group). Bone turnover markers osteocalcin (OC) and tartrate-resistant acid phosphatase 5b (TRACP 5b) were measured in serum, and bone mineral density (BMD) of the lumbar vertebrae and histomorphology of the femur were evaluated. Moreover, the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) was detected by ELISA. The expression of lipoprotein receptor-related protein (LRP) 5, β-catenin, runt-related transcription factor (Runx) 2 involving Wnt/β-catenin signalling and p38, c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases 1/2 involving mitogen-activated protein kinase signalling were determined by Western blotting.

RESULTS

The two EA-treated groups demonstrated increased levels of OC and the BMD of lumbar vertebrae, decreased levels of TRACP 5b and improved bone microstructure in the femur, compared with the untreated OVX group (P<0.05). Histomorphology analysis showed that EA treatment significantly increased the values of the trabeculae (µm), trabecular area (%) and trabecular bone number (per mm) and reduced trabecular separation (mm), compared with the OVX group. In addition, the ratio of OPG to RANKL and LRP5, β-catenin and Runx2 expression were significantly upregulated, while the expression of phosphorylated (p)-p38 and p-JNK were downregulated in EA-treated groups compared with the OVX group.

CONCLUSION

EA attenuates PMOP and it appears that the mechanism involves the regulation of multiple targets and pathways.

摘要

背景

绝经后骨质疏松症(PMOP)的发病机制复杂,涉及多种细胞信号转导通路。本研究旨在比较电针对 GV4/GV6 与 BL20/BL23 对去卵巢(OVX)大鼠骨骼的影响,以探讨电针对骨骼作用的介导途径。

方法

40 只雌性 Sprague-Dawley 大鼠随机分为 4 组(每组 10 只):假手术组(Sham 组)、OVX 手术组(OVX 组)、OVX 手术加电针对 GV4/GV6 组(GV 组)和 OVX 手术加电针对 BL20/BL23 组(BL 组)。检测血清骨转换标志物骨钙素(OC)和抗酒石酸酸性磷酸酶 5b(TRACP 5b),评估腰椎骨密度(BMD)和股骨组织形态学。此外,采用 ELISA 法检测核因子κB 受体激活剂配体(RANKL)和骨保护素(OPG)的表达。采用 Western blot 法检测脂蛋白受体相关蛋白(LRP)5、β-连环蛋白(β-catenin)、 runt 相关转录因子 2(Runx)2 涉及 Wnt/β-catenin 信号通路和 p38、c-Jun N 末端激酶(JNK)和细胞外调节蛋白激酶 1/2 涉及丝裂原激活蛋白激酶信号通路的表达。

结果

与未治疗的 OVX 组相比,两种电针治疗组的 OC 水平升高,腰椎 BMD 升高,TRACP 5b 水平降低,股骨骨微结构改善(P<0.05)。组织形态学分析表明,与 OVX 组相比,电针治疗组的小梁(µm)、小梁面积(%)和小梁数(每毫米)显著增加,而小梁分离(mm)显著减少。此外,与 OVX 组相比,电针治疗组 OPG 与 RANKL 的比值以及 LRP5、β-catenin 和 Runx2 的表达显著上调,而磷酸化(p)-p38 和 p-JNK 的表达下调。

结论

电针可减轻 PMOP,其机制可能涉及多个靶点和途径的调节。

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