雷公藤甲素防治青光眼术后滤过泡纤维化的可行性分析

青光眼滤过术是目前青光眼的主要治疗手段，滤过泡纤维化是导致治疗失败的主要原因。滤过泡纤维化是一种临床常见的纤维增生性病变，与成纤维细胞活化增殖及产生大量胶原蛋白等细胞外基质（ECM）有关。目前临床上防治滤过泡纤维化的药物主要是5-氟尿嘧啶（5-FU）和丝裂霉素C（MMC），它们虽也有一定疗效，但存在着不同程度的副作用而限制了临床使用。雷公藤甲素（TPL）是中药雷公藤的主要活性成分，具有免疫抑制、抗炎、抗肿瘤、抗生育等多种药理作用。系统综述近十年发表的相关文献，我们认为TPL可能具有防治青光眼术后滤过泡纤维化的功效，这与其具有的三方面作用有关：（1）抑制成纤维细胞活化增殖及胶原蛋白合成；（2）减轻创伤后炎症反应，从而抑制术后纤维瘢痕形成；（3）对视网膜神经节细胞（RGCs）有一定的保护作用。TPL抗滤过泡纤维化作用机制可能与其抑制TGF-β/Smad、NF-κB及PI3K/AKT通路有关。本文对TPL防治青光眼术后滤过泡纤维化的可行性进行了充分的分析，对于我们开发新的抗滤过泡纤维化药物及拓展TPL的临床应用具有一定的指导意义。

Feasibility analysis of Triptolide's role in treating filtering bleb fibrosis after the filtration surgery of glaucoma

At present, filtration surgery remains an important treatment of glaucoma, and filtering bleb fibrosis is the main cause for treatment failure. Filtering bleb fibrosis is a common fiber hyperplastic disease, and it relates to the activation and proliferation of fibroblasts and the excessive production of extracellular matrix（ECM）such as collagen protein. The most frequently-used drugs for filtering bleb fibrosis in clinic are 5-fluoro-2,4（1h, 3h）pyrimidinedione（5-Fu）and mitomycin（MMC）. Although they are effective in some degree, they also have some serious side effects which restrict their clinical use. Triptolide（TPL）is a major active component of the medicinal plant, tripterygium wilfordii hook.f.（TWHF）. TPL has multiple pharmacological activities including immunosuppressive, anti-inflammatory, anti-cancer and anti-fertility activity. Reviewing related literatures published in recent ten years, we confirmed that TPL seemed to possess a pharmacological activity in treating filtering bleb fibrosis. Since it has three major functions： 1. inhibit the activation and proliferation of fibroblasts and the excessive production of collagen protein; 2. alleviate the inflammatory reaction after surgical wound to suppress fibrous scar formation; 3.TPL has a protective effect on retinal ganglion cells（RGCs）. We further find that TPL＇s anti-fibrosis activity mainly results from that it inhibits TGF-β/Smad,NF-κB and PI3K/AKT signal transduction pathway. This comprehensive analysis about the feasibility of Triptolide＇s role in treating filtering bleb fibrosis after the filtration surgery of glaucoma can help us develop new drugs for filtering bleb fibrosis and exploit TPL＇s clinical value on some level.