Yin Yuesong, Hu Hai, Yang Yian, Wu Song
Orthopedics Department, The Third Xiangya Hospital of Central South University, No.138 Tongzipo Road, Yuelu District, Changsha, 410013, China.
Oncology Department, The Third Xiangya Hospital of Central South University, Changsha, 410013, China.
Mol Med. 2024 Dec 2;30(1):240. doi: 10.1186/s10020-024-01009-0.
Rotator cuff tears (RCTs) are among the most common musculoskeletal disorders that affect quality of life. This study aimed to investigate the efficacy of ginsenoside Rb1 in RCTs and the mechanisms involved.
First, a fibrotic model of FAPs was induced, and FAPs were cultured in media supplemented with different concentrations of ginsenoside Rb1. Next, a rat model of RCTs was constructed and treated with ginsenoside Rb1. Molecular docking was subsequently utilized to detect the binding of ginsenoside Rb1 and SFRP1. Finally, SFRP1 was knocked down and overexpressed in vivo and in vitro to investigate the mechanism of ginsenoside Rb1 and SFRP1 in RCTs.
Compared with the Normal group, FAP viability was decreased, but Collagen II, FN and α-SMA levels were increased in the Control group. After treatment with different concentrations of ginsenoside Rb1, FAP viability increased, but Collagen II, FN and α-SMA levels decreased. Among them, 60 µM ginsenoside Rb1 had the best effect. In vivo experiments revealed that ginsenoside Rb1 improved RCTs in rats. Molecular docking revealed the binding of ginsenoside Rb1 to SFRP1. Additionally, SFRP1 levels were lower in the Control group than in the Normal group. After treatment with ginsenoside Rb1, SFRP1 levels increased. In vivo, overexpressing SFRP1 along with ginsenoside Rb1 treatment further alleviated tendon tissue fibroblast infiltration and fat accumulation and further reduced the expression of Collagen II, FN, and α-SMA. In vitro, overexpressing SFRP1 along with ginsenoside Rb1 treatment further decreased the expression of CaMKII, PLC, PKC, Wnt, and β-catenin, further decreased the Ca fluorescence intensity and mitochondrial length, increased the red/green intensity, and decreased the MitoSOX fluorescence intensity. Additionally, overexpressing SFRP1 along with ginsenoside Rb1 treatment further increased cell proliferation, decreased apoptosis, reduced the protein expression of Collagen II, FN, and α-SMA in muscle tissue, and further reduced the levels of TNF-α, IL-1β, and IL-6 in the cell supernatant.
Ginsenoside Rb1 inhibited the activation of the Wnt signaling pathway by promoting SFRP1 expression, thereby inhibiting mitochondrial function and Ca absorption to treat fat infiltration and muscle fibrosis caused by RCTs.
肩袖撕裂（RCTs）是影响生活质量的最常见肌肉骨骼疾病之一。本研究旨在探讨人参皂苷Rb1对RCTs的疗效及其相关机制。
首先，诱导成纤维脂肪祖细胞（FAPs）纤维化模型，并将FAPs在添加不同浓度人参皂苷Rb1的培养基中培养。接下来，构建RCTs大鼠模型并用人参皂苷Rb1进行治疗。随后利用分子对接检测人参皂苷Rb1与分泌型卷曲相关蛋白1（SFRP1）的结合情况。最后，在体内和体外敲低并过表达SFRP1，以研究人参皂苷Rb1和SFRP1在RCTs中的作用机制。
与正常组相比，对照组FAPs活力降低，但Ⅱ型胶原蛋白、纤连蛋白（FN）和α-平滑肌肌动蛋白（α-SMA）水平升高。用不同浓度人参皂苷Rb1处理后，FAPs活力升高，但Ⅱ型胶原蛋白、FN和α-SMA水平降低。其中，60 μM人参皂苷Rb1效果最佳。体内实验表明人参皂苷Rb1改善了大鼠的RCTs。分子对接显示人参皂苷Rb1与SFRP1结合。此外，对照组SFRP1水平低于正常组。用人参皂苷Rb1处理后，SFRP1水平升高。在体内，与用人参皂苷Rb1治疗同时过表达SFRP1进一步减轻了肌腱组织成纤维细胞浸润和脂肪堆积，并进一步降低了Ⅱ型胶原蛋白、FN和α-SMA的表达。在体外，与用人参皂苷Rb1治疗同时过表达SFRP1进一步降低了钙/钙调蛋白依赖性蛋白激酶Ⅱ（CaMKII）、磷脂酶C（PLC）、蛋白激酶C（PKC）、Wnt和β-连环蛋白的表达，进一步降低了钙荧光强度和线粒体长度，增加了红/绿荧光强度，并降低了线粒体超氧化物荧光强度。此外，与用人参皂苷Rb1治疗同时过表达SFRP1进一步增加了细胞增殖，减少了细胞凋亡，降低了肌肉组织中Ⅱ型胶原蛋白、FN和α-SMA的蛋白表达，并进一步降低了细胞上清液中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的水平。
人参皂苷Rb1通过促进SFRP1表达抑制Wnt信号通路的激活，从而抑制线粒体功能和钙吸收，以治疗RCTs引起的脂肪浸润和肌肉纤维化。
