目的 探讨伤科益肾壮骨丸调节 Hippo-Yes 相关蛋白（YAP）/PDZ 结合转录共激活因子（TAZ）通路对膝骨 关节炎（KOA）大鼠软骨形态的影响。方法 将 SD 大鼠随机分为假手术组、模型组、模型+伤科益肾壮骨丸 （0.5 g·kg-1 ）组、模型+伤科益肾壮骨丸+si-NC 组和模型+伤科益肾壮骨丸+si-LATS 组，每组 8 只大鼠。进行大鼠 膝骨关节软骨形态观察；番红 O-固绿染色观察膝骨关节软骨组织形态；TUNEL 实验检测软骨细胞凋亡情况； 免疫组织化学染色检测 p-YAP1 表达情况；Western Blot 实验检测细胞外基质和 Hippo-YAP/TAZ 通路相关蛋白 表达。结果 与假手术组比较，模型组膝骨关节软骨呈浅黄色，关节面粗糙，出现溃烂斑点和骨赘，软骨组织 中番红 O 淡染，TUNEL 阳性率和 MMP13 表达明显升高（P＜0.05），聚集蛋白聚糖（ACAN）、抗体Ⅱ型胶原 α1 链（COL2A1）、p-大型肿瘤抑制激酶 1/2（p-LATS1/2）、p-YAP1 和 TAZ 表达明显降低（P＜0.05）；与模型组比 较，模型+伤科益肾壮骨丸组及模型+伤科益肾壮骨丸+si-NC 组膝骨关节软骨呈乳白色，关节面光滑、无裂纹、 无骨赘，软骨组织红染，TUNEL 阳性率和 MMP13 表达明显降低（P＜0.05），ACAN、COL2A1、p-LATS1/2、 p-YAP1 和 TAZ 表达明显升高（P＜0.05），且模型+伤科益肾壮骨丸组与模型+伤科益肾壮骨丸+si-NC 组的差异 无统计学意义（P＞0.05）；与模型+伤科益肾壮骨丸+si-NC 组比较，模型+伤科益肾壮骨丸+si-LATS 组膝骨关节 软骨呈浅黄色，关节面粗糙、溃烂，番红 O 淡染，TUNEL 阳性率和 MMP13 表达明显升高（P＜0.05），ACAN、 COL2A1、p-LATS1/2、p-YAP1 和 TAZ 表达明显降低（P＜0.05）。结论 伤科益肾壮骨丸可能通过调控 HippoYAP/TAZ 通路中关键蛋白的表达，维持软骨正常形态和细胞外基质平衡，缓解膝骨关节炎大鼠膝骨关节软骨 退化及损伤。

Objective To investigate the effects of Shangke Yishen Zhuanggu Pills on cartilage morphology in rats with knee osteoarthritis （KOA） by regulating the Hippo-YAP/TAZ pathway. Methods SD successfully modeled SD rats were divided into sham-operated group，model group，model+Shangke Yishen Zhuanggu Pills （0.5 g·kg-1 ） group，model+ Shangke Yishen Zhuanggu Pills+si-NC group，and model+Shangke Yishen Zhuanggu Pills+si-LATS group，with 8 rats in each group. Morphological observation of rat knee articular cartilage was performed；Safranin O-Fast Green staining was used to observe the histomorphology of knee articular cartilage；TUNEL assay was conducted to detect chondrocyte apoptosis；immunohistochemical staining was performed to detect p-YAP1 expression；Western Blot was used to detect the expression of extracellular matrix and Hippo-YAP/TAZ pathway-related proteins. Results Compared with the shamoperated group，the knee articular cartilage in the model group appeared light yellow with a rough articular surface， ulcerated spots， and osteophytes； cartilage tissue showed pale Safranin O staining； the TUNEL-positive rate and MMP13 expression were significantly increased （P＜0.05）； while the expressions of Aggrecan （ACAN）， Collagen type Ⅱ α1 chain （COL2A1）， p-Large tumor suppressor kinase 1/2 （p-LATS1/2）， p-YAP1， and TAZ were significantly decreased （P＜0.05）. Compared with the model group，the knee articular cartilage in the model+Shangke Yishen Zhuanggu Pills group and the model + Shangke Yishen Zhuanggu Pills+si-NC group appeared milky white with a smooth articular surface，no cracks，and no osteophytes；cartilage tissue showed red staining；the TUNEL-positive rate and MMP13 expression were significantly decreased （P＜0.05）； while the expressions of ACAN， COL2A1， p-LATS1/2， p-YAP1， and TAZ were significantly increased （P＜0.05）； moreover， there was no statistically significant difference between the model+Shangke Yishen Zhuanggu Pills group and the model+Shangke Yishen Zhuanggu Pills+si-NC group （P＞0.05）. Compared with the model+Shangke Yishen Zhuanggu Pills+si-NC group，the knee articular cartilage in the model+Shangke Yishen Zhuanggu Pills+si-LATS group appeared light yellow with a rough， ulcerated articular surface； Safranin O staining was pale； the TUNEL-positive rate and MMP13 expression were significantly increased （P＜0.05）；while the expressions of ACAN，COL2A1，p-LATS1/2，p-YAP1，and TAZ were significantly decreased （P＜0.05）. Conclusion Shangke Yishen Zhuanggu Pills may alleviate knee articular cartilage degeneration and injury in rats with knee osteoarthritis by regulating the expression of key proteins in the Hippo-YAP/ TAZ pathway，thereby maintaining normal cartilage morphology and extracellular matrix homeostasis.

R285.5

湖北省自然科学基金项目（2024AFD348）；湖北省时珍人才工程科研项目（鄂卫函[2024]256 号）；湖北省中医药管理局科研项目 （ZY2025L015）；荆州市科学技术局项目（2025HD131）。