| 刘锋,何智军,林知毅,等.治骨疏松膏防治绝经后骨质疏松症的作用及机制[J].安徽医药,2026,30(11):2189-2193. |
| 治骨疏松膏防治绝经后骨质疏松症的作用及机制 |
| Effect and mechanism of Zhigushusong ointment on the prevention and treatment of postmenopausal osteoporosis |
| |
| DOI：10.3969/j.issn.1009-6469.2026.11.013 |
| 中文关键词: 骨质疏松，绝经后 线粒体未折叠蛋白反应 氧化应激 治骨疏松膏 |
| 英文关键词: Osteoporosis,postmenopausal Mitochondrial unfolded protein response Oxidative stress Zhigushusong ointment |
| 基金项目:广东省中医药管理局科研项目( 20241227) |
|
| 摘要点击次数: 0 |
| 全文下载次数: 0 |
| 中文摘要: |
| 目的从线粒体未折叠蛋白反应( UPRmt)的角度探讨治骨疏松膏防治绝经后骨质疏松( POMP)的机制，为中医药防治 POMP提供实验依据。方法 2024年 1―5月采用卵巢切除法构建 POMP大鼠模型，并将 48只 SD大鼠采用随机数字表法分为假手术组、模型组、中药组、雌激素组。使用 micro CT对药物干预 12周后离体股骨进行结构分析，使用实时荧光定量多聚酶链式反应( qRT-PCR)检测 UPRmt相关分子热休克蛋白 60(Hsp60)、酪蛋白裂解酶 P(ClpP)以及 ER α-NRF1-HTRA2轴相关分子雌激素受体 -α(Erα)、蛋白激酶 B(AKT)、线粒体调节剂核呼吸因子 1(NRF1)线粒体膜间隙蛋白酶(HTRA2)的 mRNA水平，并使用蛋白质印迹法检测相应蛋白水平。结果与假手术组相比，模型组的相、对骨体积( Tb.BV/TV)［( 8.52±1.23)%比( 25.34± 2.10)%］、骨小梁数目( Tb.N)［( 0.85±0.12)/mm比( 2.56±0.21)/mm)］、骨小梁密度( Tb.BMD)［( 0.12±0.02)g/cm3比( 0.35±0.03)g/ cm3］和骨小梁厚度( Tb.Th)［(0.045±0.005)mm比( 0.078±0.006)mm］均显著降低(均 P<0.05)而骨小梁分离度( Tb.Sp)［( 0.68± 0.05)mm比( 0.38±0.04)mm)］显著升高( P<0.01)。与模型组相比，中药组的 Tb.BV/TV(21.15±1.8，5)%、Tb.N(2.21±0.18)/mm、Tb. BMD(0.30±0.02)g/cm3和 Tb.Th(0.072±0.006)mm均显著升高(均 P<0.05)，Tb.Sp(0.42±0.04)mm显著降低( P<0.05)，且中药组上述指标改善均优于雌激素组(均 P<0.05)。模型组 Hsp60 0.45±0.05和 ClpP 0.52±0.06的表达水平显著低于假手术组 1.00±0.08(均 P<0.05)，而中药组 Hsp60 0.86±0.07和 ClpP 0.91±0.08的表达水平显著高于模型组(均 P<0.05)，且显著高于雌激素组(均 P<0.05)。模型组 Erα、AKT、NRF1及 HTRA2的 mRNA和蛋白水平均显著低于假手术组(均 P<0.05)，而中药组上述指标水平均显著高于模型组(均 P<0.05)且显著高于雌激素组(均 P<0.05)。结论治骨疏松膏具有防治绝经后骨质疏松的作用，能显著改善去卵巢大鼠的骨微结构，机制可能与上调 ERα-NRF1-HTRA2/蛋白酶体途径、促进 UPRmt有关。其， |
| 英文摘要: |
| Objective To explore the mechanism of Zhigushusong ointment in preventing and treating postmenopausal osteoporosis(POMP) from the perspective of mitochondrial unfolded protein response (UPRmt), providing experimental evidence for the use of tradi-tional Chinese medicine.Methods From January to May 2024, a POMP rat model was established by ovariectomy, and 48 SD ratswere randomly divided into sham surgery group, model group, estrogen group, and Chinese medicine group. Micro-CT was used to ana-lyze the bone structure of excised femurs after 12 weeks of intervention. Real-time quantitative polymerase chain reaction (qRT-PCR) was performed to detect the mRNA levels of UPRmt-related molecules [heat shock protein 60 (Hsp60) and caseinolytic protease P (ClpP)] and ERα-NRF1-HTRA2 axis-related molecules [estrogen receptor-α (Erα), protein kinase B (AKT), nuclear respiratory factor 1 (NRF1), and high-temperature requirement protein A2 (HTRA2)]. Western blotting was used to detect the corresponding protein levels. Results Compared with the sham group, the model group showed significantly lower trabecular bone volume fraction (Tb. BV/TV)[(8.52±1.23) % vs. (25.34±2.10) %], trabecular number (Tb.N) [(0.85±0.12)/mm vs. (2.56±0.21)/mm], trabecular bone mineral density (Tb.BMD) [(0.12±0.02) g/cm3 vs. (0.35±0.03) g/cm3], and trabecular thickness (Tb.Th)[(0.045±0.005) mm vs. (0.078±0.006) mm] (all P< 0.05), and significantly higher trabecular separation (Tb.Sp) [(0.68±0.05) mm vs. (0.38±0.04) mm] (P<0.01). Compared with the modelgroup, the Chinese medicine group showed significantly increased Tb.BV/TV, Tb.N, Tb.BMD, and Tb.Th [(21.15±1.85) %, (2.21±0.18)/mm, (0.30±0.02) g/cm3, and (0.072±0.006) mm, respectively] and decreased Tb.Sp [(0.42±0.04) mm, all P<0.05], with better improve-ments than the estrogen group (all P<0.05). The mRNA and protein levels of Hsp60 [(0.45±0.05) vs. (1.00±0.08)] and ClpP [(0.52±0.06) vs. (1.00±0.09)] in the model group were significantly lower than those in the sham group (all P<0.05), while the expression levels in theChinese medicine group [(0.86±0.07) and (0.91±0.08), respectively] were significantly higher than those in the model group (all P< 0.05) and the estrogen group (all P<0.05). The mRNA and protein levels of Erα, AKT, NRF1, and HTRA2 in the model group were sig-nificantly lower than those in the sham group (all P<0.05), while the expression levels in the Chinese medicine group were significantly higher than those in the model group (all P<0.05) and the estrogen group (all P<0.05).Conclusion Zhigushusong ointment has a pre-ventive and therapeutic effect on POMP, significantly improving the bone microarchitecture of ovariectomized rats, possibly through up‐regulating the ERα-NRF1-HTRA2/proteasome pathway and promoting UPRmt. |
|
查看全文
查看/发表评论 下载PDF阅读器 |
| 关闭 |
|
|
|
