基于PI3K/AKT/mTOR信号通路探讨积雪草水提物联合碳硅橡胶在治疗包膜挛缩中的作用与机制研究

The abnormal proliferation of fibroblasts on the surface of the implanted material is the most important factor leading to the capsular contracture. Previous studies have showed that carbon silicone rubber can treat it by inhibiting the abnormal proliferation, but the therapeutic effect is not very ideal. Then the research group made joint application of asiatiside and carbon silicone rubber, finding that proliferation of fibroblasts on the material surface was inhibited effectively, and thus achieved the treatment of capsular contracture. Meanwhile, the protein expression of p-mTOR, α-SMA and cyclin decreased. The mTOR is downstream molecule of PI3K/AKT and it can regulate cell proliferation. Therefore, it is presumed that asiatiside may inhibit the abnormal proliferation of fibroblasts by inhibiting the signaling pathway of PI3K/AKT/mTOR. In this study, we try to discuss the important role of PI3K/AKT/mTOR signaling pathway in the inhibition of fibroblasts’ abnormal proliferation through in vivo / in vitro experiments. The project has found that the combined application of asiaticoside and carbon silicone rubber can play a role in the treatment of capsule contracture. At the same time, its molecular mechanism is also in the discussion, which provides an important theoretical basis for exploring the wider Western use of asiaticoside in the field of traditional Chinese medicine.

成纤维细胞在植入材料表面的异常增殖是导致包膜挛缩症最主要因素。前期研究发现碳硅橡胶能通过抑制成纤维细胞异常增殖从而治疗包膜挛缩，但治疗效果并不十分理想。随后课题组将积雪草水提物与碳硅橡胶进行联合应用，发现成纤维细胞在材料表面的增殖得到了有效的抑制，从而达到治疗包膜挛缩的作用；同时p-mTOR、α-SMA、cyclin等蛋白表达出现下调，mTOR是PI3K/AKT下游分子，且具有调控细胞增殖的作用。故推测积雪草水提物可能通过抑制PI3K/AKT/mTOR信号通路达到阻抑成纤维细胞异常增殖的目的。本研究拟采用在体/离体实验探讨PI3K/AKT/mTOR信号通路在积雪草水提物抑制成纤维细胞增殖中的重要作用。该项目前期发现了积雪草水提物与碳硅橡胶的联合应用能起到治疗包膜挛缩的作用，同时对其分子机制进行探讨，为发掘积雪草水提物更广阔的“中药西用”领域提供重要理论基础。

成纤维细胞在植入材料表面的异常增殖是导致包膜挛缩症最主要因素。前期研究发现碳硅 橡胶能通过抑制成纤维细胞异常增殖从而治疗包膜挛缩，但治疗效果并不理想。随后课题组将积雪草水提物与碳硅橡胶进行联合应用，发现成纤维细胞在材料表面的增殖得到了有效的 抑制，从而达到治疗包膜挛缩的作用。结合前期研究基础，本项目成功构建出大鼠体内包膜挛缩模型，采用积雪草苷药物处理，探究积雪草苷对成纤维细胞的增殖行为调控，同时探究其相关分子机制。研究结果发现积雪草苷通过PI3K信号通路对成纤维细胞的增殖行为进行调控，同时我们也发现积雪草苷通过TGF-b信号通路影响成纤维细胞增殖行为，并调控包膜形成。该项目前期证实积雪草水提物与碳硅橡胶的联合应用能起到治疗包膜挛缩的作用，同时对其分子机制进行探讨，为发掘积雪草水提物更广阔的“中药西用”领域提供重要理论基础。