补肾化痰方调控β2AR/cAMP-PKA-CREB通路减轻去卵巢大鼠骨质疏松*

doi:10.3870/j.issn.1672-0741.25.07.012

华中科技大学学报（医学版） ›› 2026, Vol. 55 ›› Issue (2): 220-225.doi: 10.3870/j.issn.1672-0741.25.07.012

补肾化痰方调控β₂AR/cAMP-PKA-CREB通路减轻去卵巢大鼠骨质疏松^*

张麟¹, 陈之浩², 杨硕硕², 陈驰², 周广文^2△

¹武汉市中西医结合医院/武汉市第一医院骨科,武汉 430022
²湖北中医药大学针灸骨伤学院,武汉 430065

出版日期:2026-04-15 发布日期:2026-04-16
通讯作者: ^△E-mail:609053257@qq.com
作者简介:张麟,男,1987年生,主治医师,E-mail:631612645@qq.com
基金资助:
^*武汉市卫生健康委员会医学科研项目(No.WZ19Q03);湖北省自然科学基金中医药创新发展联合基金项目(No.2024AFD296); 湖北省卫生健康委中医药联合基金项目(No.ZY2025L222)

Effects of Bushen Huatan Decoction on the β₂AR/cAMP-PKA-CREB Signaling Pathway in a Rat Model of Postmenopausal Osteoporosis

Zhang Lin¹, Chen Zhihao², Yang Shuoshuo² et al

¹Department of Orthopedics and Joint Surgery,Wuhan Hospital of Traditional Chinese and Western Medicine/Wuhan No.1 Hospital,Wuhan 430022,China
²College of Acupuncture-Moxibustion and Orthopedics,Hubei University of Chinese Medicine,Wuhan 430065,China

Online:2026-04-15 Published:2026-04-16
Contact: ^△E-mail:609053257@qq.com

摘要/Abstract

摘要： 目的研究补肾化痰方(BSHT)对绝经后骨质疏松症模型大鼠环磷酸腺苷(cAMP)-蛋白激酶A(PKA)-cAMP效应元件结合蛋白(CREB)信号通路及β₂肾上腺素能受体(β₂ adrenergic receptor,β₂AR)通路的影响。方法取SD大鼠30只,随机分为假手术(Sham)组、模型(OVX)组、BSHT组,每组10只,去卵巢法复制绝经后骨质疏松模型。从造模后第5周开始,各组分别以生理盐水(Sham组和OVX组)或BSHT药液(BSHT组)灌胃;于造模第12周末处死大鼠,取材后进行指标检测。采用微型计算机断层扫描技术(micro CT)检测大鼠股骨的微结构;采用逆转录聚合酶链反应(RT-PCR)和蛋白质印迹法(Western blot)检测骨组织中相关信号通路分子,如β₂AR、PKA、CREB的基因和蛋白表达水平;采用免疫组织化学法(immunohistochemistry,IHC)检测蛋白的组织定位。结果与Sham组相比,OVX组大鼠的骨微结构指标,包括骨密度(bone mineral density,BMD)、骨体积分数(bone volume fraction,BV/TV)、骨小梁厚度(trabecular thickness,Tb.Th)、骨小梁数量(trabecular number,Tb.N)均明显下降,骨小梁分离度(trabecular separation,Tb.Sp)升高;信号通路指标中,PKA、CREB的mRNA及蛋白表达水平明显下降,β₂AR mRNA及蛋白表达明显增加(均P<0.05)。与OVX组相比,BSHT组大鼠的骨微结构相关指标(BMD、BV/TV、Tb.Th、Tb.N)及PKA、CREB表达明显增加,而Tb.Sp、β₂AR表达水平明显下降(均P<0.05)。IHC结果显示骨小梁周边的成骨细胞和骨髓基质细胞的胞质中,β₂AR、PKA、CREB呈阳性表达。结论 BSHT能够通过调节去势骨质疏松症大鼠β₂AR及cAMP-PKA-CREB信号通路,影响骨重建,从而起到防治骨质疏松的作用。

关键词: 补肾化痰方, β₂肾上腺素能受体, cAMP-PKA-CREB信号通路, 绝经后骨质疏松症

Abstract: Objective To investigate the effects of Bushen Huatan decoction(BSHT) on the β₂ adrenergic receptor(β₂AR)and the cyclic AMP(cAMP)-protein kinase A(PKA)-cAMP response element binding protein(CREB)signaling pathway in ovariectomized rats. Methods A postmenopausal osteoporosis rat model was established by ovariectomy.30 rats were randomly divided into 3 groups:A sham operation (Sham)group,a model (OVX)group,and a (BSHT)group.5 weeks after the operation,the rats received different treatments(4 mL of normal saline for the Sham and OVX groups,and BSHT for the BSHT group).Micro-computed tomography(micro CT)was used to assess the microstructure of the femur.The mRNA and protein expression levels of β₂AR,PKA,and CREB in the femur were detected by RT-PCR and Western blotting,respectively.The distribution of the proteins in femur tissue was determined by immunohistochemistry(IHC). Results Compared with the Sham group,the OVX group showed significantly decreased bone mineral density(BMD),bone volume fraction(BV/TV),trabecular thickness(Tb.Th),and trabecular number(Tb.N),as well as increased trabecular separation(Tb.Sp).The mRNA and protein levels of PKA and CREB were also decreased,while the mRNA and protein levels of β₂AR were significantly increased(all P<0.05)in the OVX group.Compared with the OVX group,the BSHT group exhibited significantly increased BMD,BV/TV,Tb.Th,Tb.N,and expression levels of PKA and CREB,along with significantly decreased expression levels of β₂AR(all P<0.05).IHC results showed that β₂AR,PKA,and CREB were positively expressed in the cytoplasm of osteoblasts surrounding the trabeculae and in bone marrow stromal cells. Conclusion BSHT may prevent and treat osteoporosis in ovariectomized rats by regulating the expression of β₂AR and the cAMP-PKA-CREB signaling pathway.

Key words: Bushen Huatan decoction, β₂AR, cAMP-PKA-CREB signaling pathway, postmenopausal osteoporosis

中图分类号:

R285.5

张麟, 陈之浩, 杨硕硕, 陈驰, 周广文. 补肾化痰方调控β₂AR/cAMP-PKA-CREB通路减轻去卵巢大鼠骨质疏松^*[J]. 华中科技大学学报（医学版）, 2026, 55(2): 220-225.

Zhang Lin, Chen Zhihao, Yang Shuoshuo et al. Effects of Bushen Huatan Decoction on the β₂AR/cAMP-PKA-CREB Signaling Pathway in a Rat Model of Postmenopausal Osteoporosis[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(2): 220-225.

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补肾化痰方调控β₂AR/cAMP-PKA-CREB通路减轻去卵巢大鼠骨质疏松^*

Effects of Bushen Huatan Decoction on the β₂AR/cAMP-PKA-CREB Signaling Pathway in a Rat Model of Postmenopausal Osteoporosis

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