姜黄素通过TLR4/BAMBI/TGF-β信号通路抑制前列腺增生的作用及机制研究

Histological inflammation in the development of benign prostatic hyperplasia (BPH) has attracted widespread attention and also a hot-spot in current researches. In our previous study, we found that TLR4-dependent downregulation of BAMBI might be an important mechanism of TLR4 activation intensifying TGF-β-mediated EMT. Numerous studies showed that anti-inflammatory drugs obtained from natural products having the low toxicity are the very effective means for BPH. Curcumin is reported to have anti-inflammatory, antioxidant and anti-fibrosis properties. Our previous work found that the Curcumin can inhibit EMT and prostate hyperplasia in vivo, suggesting Curcumin is expected to become a very important inhibitory effect on BPH development, but the mechanisms are unclear. On the basis of the above findings, we propose hypothesis that Curcumin might downregulate BAMBI through the TLR4/MyD88/NF-κβ signalling pathway and block the TGF-β/Smad-EMT signalling to inhibit BPH. The proposed research is significant because by revealing the mechanisms on how Curcumin affect the proliferation, apoptosis and differentiation of BPH cells, targets can be selected for future treatment to interrupt the process of EMT in the BPH.

炎症在前列腺增生（BPH）发生发展中的重要作用已引起广泛关注，是当前研究BPH发病机制的热点。我们的前期研究证实，LPS/TLR4通过下调BAMBI增强TGF-β/Smad信号介导BPH上皮细胞发生EMT。低毒的抗BPH植物制剂由于疗效好副作用小而逐渐受到重视。姜黄素（Cur）具有抗炎、抗氧化、抗纤维化等多重作用。我们的预实验结果表明Cur能抑制大鼠BPH模型，提示Cur有望成为防治BPH重要的辅助药物，但其分子机制尚不清楚。本项目在原有研究基础上，提出Cur通过抑制TLR4/MyD88/NF-κβ信号上调BAMBI，阻滞TGF-β/Smad-EMT信号激活，从而抑制BPH发生发展的假说。具体将研究Cur对前列腺内不同细胞增殖、凋亡和分化的影响，探讨Cur抑制前列腺组织EMT的分子机制，并通过构建炎症反应性大鼠BPH模型进行验证。本项目的实施将为Cur治疗BPH提供理论依据。

炎症在前列腺增生（BPH）发生发展中的重要作用已引起广泛关注，是当前研究BPH发病机制的热点。姜黄素（Cur）具有抗炎、抗氧化、抗纤维化等多重作用。我们旨在探究姜黄素是否缓解炎性前列腺增生，明确其是否通过调控TLR4/BAMBI/TGF-β1信号通路抑制前列腺上皮细胞的EMT过程，并寻求其具体的作用靶点。在本研究中，我们通过建立小鼠炎性前列腺增生模型和LPS+TGF-β1联合诱导人前列腺增生上皮细胞系（BPH-1）模型来探讨姜黄素在体内及体外抗炎和抗EMT的机制。结果表明，姜黄素可以通过减少炎症细胞对前列腺组织的浸润起到抗炎的作用，同时姜黄素通过上调TLR4/BAMBI/TGF-β1信号通路中BAMBI蛋白的表达从而抑制前列腺上皮细胞的EMT过程。本项目的顺利实施，有助于揭示姜黄素抑制BPH的分子靶点和相关机制，为开发该药的临床应用价值提供理论依据。