Xi Hong-Zhong, Chen Hao, He Shuai, Song Wei, Fu Jia-Hao, DU Bin, Liu Xin
Department of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing 210029, China.
Zhongguo Zhong Yao Za Zhi. 2025 Jun;50(12):3356-3367. doi: 10.19540/j.cnki.cjcmm.20250307.401.
This study aims to investigate the pharmacological effects and mechanisms of Yougui Yin in treating glucocorticoid-induced osteonecrosis. A rat model of glucocorticoid-associated osteonecrosis of the femoral head(GA-ONFH) was established by intramuscular injection of dexamethasone at 20 mg·kg(-1) every other day for 8 weeks. Rats were randomly allocated into control, model, and low-and high-dose(1.5 and 3.0 g·kg(-1), respectively) Yougui Yin groups. After modeling, rats in Yougui Yin groups were administrated with Yougui Yin via gavage, which was followed by femoral specimen collection. Hematoxylin-eosin staining was employed to observe femoral head repair, and immunofluorescence was employed to assess adipogenic differentiation of bone marrow mesenchymal stem cells(BMSCs) within the femoral head. Cell experiments were carried out with dexamethasone(1 μmol·L~(-1))-treated BMSCs to evaluate the effects of Yougui Yin-medicated serum on adipogenic differentiation. Animal experiments demonstrated that compared with the model group, Yougui Yin at both high and low doses significantly improved bone mineral density(BMD), bone volume/total volume(BV/TV) ratio, and trabecular thickness(Tb.Th) in the femoral head. Additionally, Yougui Yin alleviated necrosis-like changes and adipocyte infiltration and significantly reduced the expression level of peroxisome proliferator-activated receptor γ(PPARγ) in the femoral head, thereby suppressing the adipogenic differentiation of BMSCs in GA-ONFH rats. The cell experiments revealed that Yougui Yin-medicated serum markedly inhibited dexamethasone-induced adipogenic differentiation of BMSCs and down-regulated the level of PPARγ. The overexpression of PPARγ attenuated the inhibitory effect of Yougui Yin-medicated serum on the adipogenic differentiation of BMSCs, indicating the critical role of PPARγ in Yougui Yin-mediated suppression of adipogenic differentiation of BMSCs. In conclusion, Yougui Yin exerts therapeutic effects on glucocorticoid-induced osteonecrosis by down-regulating PPARγ expression and inhibiting adipogenic differentiation of BMSCs.
本研究旨在探讨右归丸治疗糖皮质激素性骨坏死的药理作用及机制。通过每隔一天肌肉注射20mg·kg⁻¹地塞米松，持续8周，建立糖皮质激素相关性股骨头坏死（GA-ONFH）大鼠模型。将大鼠随机分为对照组、模型组以及低剂量和高剂量（分别为1.5g·kg⁻¹和3.0g·kg⁻¹）右归丸组。造模后，右归丸组大鼠通过灌胃给予右归丸，随后采集股骨标本。采用苏木精-伊红染色观察股骨头修复情况，采用免疫荧光评估股骨头内骨髓间充质干细胞（BMSCs）的成脂分化。进行细胞实验，用1μmol·L⁻¹地塞米松处理BMSCs，以评估右归丸含药血清对成脂分化的影响。动物实验表明，与模型组相比，高剂量和低剂量右归丸均显著提高了股骨头的骨密度（BMD）、骨体积/总体积（BV/TV）比值和骨小梁厚度（Tb.Th）。此外，右归丸减轻了坏死样改变和脂肪细胞浸润，并显著降低了股骨头中过氧化物酶体增殖物激活受体γ（PPARγ）的表达水平，从而抑制了GA-ONFH大鼠BMSCs的成脂分化。细胞实验显示，右归丸含药血清显著抑制地塞米松诱导的BMSCs成脂分化，并下调PPARγ水平。PPARγ的过表达减弱了右归丸含药血清对BMSCs成脂分化的抑制作用，表明PPARγ在右归丸介导的抑制BMSCs成脂分化中起关键作用。总之，右归丸通过下调PPARγ表达和抑制BMSCs成脂分化，对糖皮质激素性骨坏死发挥治疗作用。
