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阳和汤加减对乳腺癌骨转移大鼠骨破坏的影响及机制研究
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| 篇名： | 阳和汤加减对乳腺癌骨转移大鼠骨破坏的影响及机制研究 |
| TITLE： | Study on the effect and mechanism of modified Yanghe decoction on bone destruction in rats with breast cancer bone metastasis |
| 摘要： | 目的 基于受体相互作用蛋白激酶1（RIPK1）/RIPK3通路探讨阳和汤加减对乳腺癌骨转移大鼠骨破坏的改善作用及潜在机制。方法以骨髓腔注射乳腺癌细胞悬液的方式构建乳腺癌骨转移大鼠模型，将造模成功的雌性大鼠随机分为模型组（灌胃等体积生理盐水），阳和汤加减低、中、高剂量组（分别灌胃相应药液1.30、2.60、5.20g/kg，按生药量计），阳和汤加减高剂量+si-RIPK1组（灌胃相应药液5.20g/kg，按生药量计；同时尾静脉注射RIPK1小干扰RNA），阳和汤加减高剂量+si-NC组（灌胃相应药液5.20g/kg，按生药量计；同时尾静脉注射阴性对照小干扰RNA），每组12只；另取12只健康大鼠作为对照组（灌胃等体积生理盐水）；每天给药1次，持续14d。称定各组大鼠给药前及末次给药后的体重；检测其机械性痛阈值、热痛阈值，观察其胫骨骨破坏情况、病理变化情况、破骨细胞形成情况；检测其胫骨组织中核因子κB受体活化因子（RANK）及其配体（RANKL）蛋白的阳性表达情况以及RIPK1、RIPK3、混合谱系激酶结构域样蛋白（MLKL）的磷酸化水平。结果与对照组比较，模型组大鼠胫骨组织中肿瘤细胞明显增生并弥散浸润骨髓腔，并可见大片细胞肿瘤性坏死、骨破坏严重、骨皮质变薄、骨小梁受损；其体重（给药前及末次给药后）、机械性痛阈值、热痛阈值和RIPK1、RIPK3、MLKL的磷酸化水平均显著降低，肿瘤体积、胫骨骨破坏面积占比、破骨细胞数量和RANK、RANKL蛋白阳性表达均显著升高/增多/上调（P＜0.05）；与模型组比较，阳和汤加减低、中、高剂量组大鼠胫骨组织上述病理改变均有所缓解，各定量指标均呈剂量依赖性改善（P＜0.05）。沉默RIPK1后，高剂量阳和汤加减的上述改善作用被显著减弱（P＜0.05）。结论阳和汤加减可减轻乳腺癌骨转移大鼠的骨破坏，上述作用可能与激活RIPK1/RIPK3通路有关。 |
| ABSTRACT： | OBJECTIVE To explore the improvement effect and potential mechanism of modified Yanghe decoction on bone destruction in rats with breast cancer bone metastasis based on the receptor-interacting serine/threonine-protein kinase 1 （RIPK1）/RIPK3 pathway. METHODS The rat model of breast cancer bone metastasis was established by injecting a suspension of breast cancer cells into the bone marrow cavity. The rats with successful modeling were randomly divided into a model group （intragastric administration of equal volume of normal saline）， modified Yanghe decoction low-， medium-， and high-dose groups （intragastric administration of corresponding decoction at 1.30， 2.60 and 5.20 g/kg， calculated by the dosage of crude drug）， high-dose modified Yanghe decoction+si-RIPK1 group （intragastric administration of corresponding decoction at 5.20 g/kg， calculated by the dosage of crude drug； simultaneous injection of small interfering RNA for RIPK1 via the tail vein）， and high-dose modified Yanghe decoction+si-NC group （intragastric administration of corresponding decoction at 5.20 g/kg， calculated by the dosage of crude drug； simultaneous injection of small interfering RNA for negative control via the tail vein）， with 12 rats in each group. Another 12 healthy rats were selected as the control group and were given the same volume of normal saline intragastrically， once a day， for 14 consecutive days. Body weight was measured before administration and at the end of the last administration. The mechanical pain threshold and thermal pain threshold were measured， and the bone destruction， pathological changes and osteoclast formation of the tibia were observed. The positive expression of receptor activator of nuclear factor-κB （RANK） and receptor activator of nuclear factor-κB ligand （RANKL） in the tibial tissue， as well as the phosphorylation levels of RIPK1， RIPK3 and mixed lineage kinase domain-like protein （MLKL） were detected. RESULTS Compared with the control group， the tumor cells of tibia tissues in rats of the model group showed significant proliferation and diffuse infiltration into the bone marrow cavity. Extensive areas of tumor necrosis of cells， severe bone destruction， thinning of the bone cortex， and damage to the bone trabeculae were observed. The body weight （before administration and at the end of the last administration）， mechanical pain threshold， thermal pain threshold， and the phosphorylation levels of RIPK1， RIPK3 and MLKL were decreased significantly； the tumor volume， the proportion of bone destruction area， the number of osteoclasts， and the positive expressions of RANK and RANKL were increased/up-regulated significantly （P＜0.05）. Compared with the model group， the above pathological changes in the tibial tissues of rats in modified Yanghe decoction low-， medium- and high-dose groups were all alleviated， and all quantitative indicators showed dose-dependent improvement （P＜0.05）. After silencing RIPK1， the aforementioned beneficial effects of high-dose modified Yanghe decoction were significantly weakened （P＜0.05）.CONCLUSIONSModified Yanghe decoction can alleviate bone destruction in rats with breast cancer bone metastasis. The above effect is related to the activation of the RIPK1/RIPK3 pathway. |
| 期刊： | 2026年第37卷第04期 |
| 作者： | 卢舜；蔡昂；樊婷婷；何威华 |
| AUTHORS： | LU Shun，CAI Ang，FAN Tingting，HE Weihua |
| 关键字： | 阳和汤加减；乳腺癌；骨转移；骨破坏；RIPK1/RIPK3通路 |
| KEYWORDS： | modified Yanghe decoction； breast cancer； bone metastasis； bone destruction； RIPK1/RIPK3 pathway |
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