南方医科大学学报

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (3): 666-674.doi: 10.12122/j.issn.1673-4254.2026.03.20

• 基础研究 • 上一篇    

水飞蓟宾通过诱导细胞自噬及凋亡双重机制抑制兔青光眼术后纤维化

张语洋1(), 申颖2(), 佟欣雨2, 段宇魁2, 罗云娜3, 郭文奇4   

  1. 1.内蒙古医科大学第一临床医学院，内蒙古 呼和浩特 010050
    2.内蒙古医科大学附属医院 眼视光中心，内蒙古 呼和浩特 010050
    3.内蒙古医科大学附属医院 健康管理中心，内蒙古 呼和浩特 010050
    4.内蒙古医科大学第二附属医院正骨科，内蒙古 呼和浩特 010020
  • 收稿日期:2025-07-17 出版日期:2026-03-20 发布日期:2026-03-26
  • 通讯作者: 申颖 E-mail:943304172@qq.com;shenying_abc@sohu.com
  • 作者简介:张语洋，在读硕士研究生，E-mail：943304172@qq.com
  • 基金资助:
    内蒙古自治区自然科学基金面上项目(2025MS08003);内蒙古医科大学附属医院高层次人才培养项目“航行系列”;内蒙古医科大学“致远”人才计划-“善学”人才(ZY20242131);内蒙古医科大学面上项目(YKD2022MS003);内蒙古自治区专科区域医疗中心

Silybin inhibits fibrosis after glaucoma filtration surgery in rabbits by promoting fibroblast autophagy

Yuyang ZHANG1(), Ying SHEN2(), Xinyu TONG2, Yukui DUAN2, Yunna LUO3, Wenqi GUO4   

  1. 1.First Clinical Medical College of Inner Mongolia Medical University, Hohhot 010050, China
    2.Optometry Center
    3.Health Management Center, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
    4.Department of Orthopedics, Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010020, China
  • Received:2025-07-17 Online:2026-03-20 Published:2026-03-26
  • Contact: Ying SHEN E-mail:943304172@qq.com;shenying_abc@sohu.com

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摘要：

目的 探讨水飞蓟宾在抑制青光眼术后纤维化的作用及其分子机制。 方法 体内动物实验：将25只健康新西兰兔随机分为对照组及不同浓度水飞蓟宾实验组（50、100、200、250 μmol/L），5只/组，左眼行小梁切除术后连续7 d进行结膜下注射。术后动态监测眼压和滤过泡形态（Krofeld分型），第28天取术眼组织进行HE、Masson染色，Fibronectin和Collagen I免疫荧光检测。体外实验：通过TGF-β1诱导兔Tenon囊成纤维细胞纤维化模型，结合Western blotting及流式细胞术分析水飞蓟宾对自噬（LC3II/LC3I、p62）与凋亡的调控作用。 结果 术后7~21 d，不同浓度水飞蓟宾实验组兔眼压均低于对照组（P<0.05）。200 μmol/L、250 μmol/L实验组兔眼压降低可维持至术后28 d（P<0.05）。术后14~21 d，随着水飞蓟宾浓度升高，功能性滤过泡数形成率升高（P<0.05），200、250 μmol/L水飞蓟宾组在术后28 d仍保持40%以上的功能性滤过泡（P<0.05）。HE和Masson染色显示，各实验组炎性细胞浸润程度和纤维细胞数量较对照组降低、胶原沉积呈浓度依赖性减少。免疫荧光实验显示，水飞蓟宾呈剂量依赖性减少Fibronectin与Collagen I阳性细胞数量（P<0.001）。体外实验显示，水飞蓟宾逆转TGF-β1诱导的成纤维细胞纤维化表型（P<0.01），上调LC3II/LC3I比值（P<0.0001），降低p62表达（P<0.0001），并促进细胞凋亡（P<0.0001）。 结论 水飞蓟宾可明显抑制青光眼术后纤维化，可能是通过激活细胞自噬及诱导细胞凋亡双重机制减少成纤维细胞活化。

关键词: 水飞蓟宾, 青光眼滤过术, 纤维化, 自噬, 凋亡, 兔Tenons囊成纤维细胞

Abstract:

Objective To investigate the effect of silybin in inhibiting fibrosis after glaucoma filtration surgery and the underlying mechanism. Methods Twenty-five healthy rabbits undergoing unilateral trabeculectomy on the left eye were randomly assigned into 5 groups for treatment with subconjunctival injections of sterilized water (control) or 50, 100, 200, and 250 μmol/L silybin for 7 consecutive days. Postoperative intraocular pressure (IOP) and filtration bleb morphology (Krofeld classification) were monitored. On day 28, tissues samples were harvested from the operated eyes for HE staining, Masson's trichrome staining, and immunofluorescence detection of fibronectin and collagen I. In cultured rabbit Tenon's capsule fibroblasts with TGF‑β1-induced fibrosis, the effects of silybin on autophagy and apoptosis were analyzed using Western blotting (LC3II/LC3I ratio and p62 expression) and flow cytometry. Results From postoperative day 7 to day 21, the rabbits with silybin treatment showed significantly lower IOP than those in the control group, and in the 200 and 250 μmol/L silybin groups, IOP reduction was maintained up to postoperative day 28. From postoperative day 14 to day 21, silybin dose-dependently increased the formation rate of functional filtering blebs, the 200 and 250 μmol/L silybin groups maintained more than 40% functional filtering blebs from postoperative day 14 to day 28. HE staining revealed obviously lessened inflammatory cell infiltration in silybin treatment groups compared with that in the control group. Masson's trichrome staining showed progressively reduced fibroblast numbers and collagen deposition in the silybin groups. Immunofluorescence staining confirmed that silybin dose-dependently reduced fibronectin and collagen I-positive cells. In cultured rabbit Tenon's capsule fibroblasts, silybin treatment effectively reversed TGF-β1-induced fibroblast fibrotic phenotype, increased the LC3II/LC3I ratio, decreased p62 expression, and promoted apoptosis of the fibroblasts. Conclusion Silybin significantly inhibits postoperative fibrosis in rabbit models of glaucoma likely by activating cellular autophagy and inducing apoptosis to reduce fibroblast activation.

Key words: silybin, glaucoma filtration, fibrosis, autophagy, apoptosis, rabbit Tenons capsule fibroblasts