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与丝裂霉素 C 比较,樱花皂苷对原代培养翼状胬肉成纤维细胞的抗纤维化作用。

Antifibrotic Effects of Sakuraso-Saponin in Primary Cultured Pterygium Fibroblasts in Comparison With Mitomycin C.

机构信息

Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

出版信息

Invest Ophthalmol Vis Sci. 2019 Nov 1;60(14):4784-4791. doi: 10.1167/iovs.19-27153.

Abstract

PURPOSE

To investigate the antifibrotic effects of sakuraso-saponin on a primary culture of human pterygium fibroblasts (HPFs) and normal human Tenon fibroblasts (HTFs) as compared to the effects of mitomycin C (MMC).

METHODS

Samples of HPFs and HTFs were acquired during primary pterygium surgery. Cell toxicity, cell migration, and expression of α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) were evaluated in HPFs and HTFs after treatment with sakuraso-saponin and MMC. To determine the possible mechanisms underlying the antifibrotic effects of sakuraso-saponin, the expression of phosphorylated Smad2/3 was evaluated after treatment with sakuraso-saponin and MMC.

RESULTS

MMC (≥200 μg/mL) significantly reduced cell viability in both HPFs and HTFs, whereas sakuraso-saponin (1.0 μg/mL) decreased cell viability in HPFs only. Both sakuraso-saponin (1.0 μg/mL) and MMC (200 μg/mL) treatment significantly reduced the expression of α-SMA and TGF-β in HPFs (P < 0.05). It is interesting that the expression of α-SMA and TGF-β after treatment with sakuraso-saponin was significantly lower than that after treatment with MMC (P < 0.05). The expression of phosphorylated Smad2/3 protein was decreased by sakuraso-saponin and MMC in HPFs. Both sakuraso-saponin and MMC inhibited TGF-β1-induced cell migration as compared to the control in HPFs.

CONCLUSIONS

Sakuraso-saponin could be more effective than MMC for the reduction of fibrosis in HPFs. Our results might present the basis for its use as a promising candidate drug for adjuvant therapy to prevent recurrent pterygium after surgery.

摘要

目的

与丝裂霉素 C(MMC)相比,研究樱草糖皂甙对原代培养的人翼状胬肉成纤维细胞(HPFs)和正常人眼Tenon 纤维细胞(HTFs)的抗纤维化作用。

方法

在原发性翼状胬肉手术中获取 HPFs 和 HTFs 样本。在分别用樱草糖皂甙和 MMC 处理 HPFs 和 HTFs 后,评估细胞毒性、细胞迁移以及α-平滑肌肌动蛋白(α-SMA)和转化生长因子-β(TGF-β)的表达。为了确定樱草糖皂甙抗纤维化作用的可能机制,在分别用樱草糖皂甙和 MMC 处理后,评估磷酸化 Smad2/3 的表达。

结果

MMC(≥200μg/mL)显著降低了两种细胞(HPFs 和 HTFs)的细胞活力,而樱草糖皂甙(1.0μg/mL)仅降低了 HPFs 的细胞活力。樱草糖皂甙(1.0μg/mL)和 MMC(200μg/mL)处理均显著降低了 HPFs 中α-SMA 和 TGF-β的表达(P<0.05)。有趣的是,樱草糖皂甙处理后的α-SMA 和 TGF-β表达明显低于 MMC 处理后的表达(P<0.05)。樱草糖皂甙和 MMC 均可降低 HPFs 中磷酸化 Smad2/3 蛋白的表达。与对照组相比,樱草糖皂甙和 MMC 均抑制了 TGF-β1 诱导的 HPFs 细胞迁移。

结论

樱草糖皂甙在减少 HPFs 纤维化方面可能比 MMC 更有效。我们的结果可能为其作为预防手术后翼状胬肉复发的辅助治疗有前途的候选药物提供依据。

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