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汉防己甲素在体外抑制人结膜下成纤维细胞的活化。

Tetrandrine suppresses activation of human subconjunctival fibroblasts in vitro.

作者信息

Kitano Ai, Yamanaka Osamu, Ikeda Kazuo, Ishida-Nishikawa Iku, Okada Yuka, Shirai Kumi, Saika Shizuya

机构信息

Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan.

出版信息

Curr Eye Res. 2008 Jul;33(7):559-65. doi: 10.1080/02713680802220817.

Abstract

PURPOSE

To investigate the effect of tetrandrine on activation of human subconjunctival fibroblasts (SCFs) in vitro.

METHODS

Effects of tetrandrine on proliferation, matrix expression, myofibroblast generation, and cell migration of SCF were examined in SCF cultures. Tetrandrine effect on TGFbeta 1/Smad2 signal and Smad7 expression was examined. Migration was evaluated by in vitro defect closure in a monolayer cell culture. Western blotting and immunocytochemistry were used.

RESULTS

Tetrandrine suppressed wound-induced cell migration (defect closure) and myofibroblast generation, but not cell proliferation in SCF cultures. It also decreased expression of fibronectin, collagen I, and alpha SMA. Adding tetrandrine increased protein level of Smad7 and suppressed Smad2 signal.

CONCLUSION

Tetrandrine suppresses Smad2 signal and fibrogenic responses in SCFs in association with Smad7 up-regulation, suggesting its potential therapeutic value to prevent excess scarring/fibrosis in conjunctiva following trabeculectomy or in patients with severe conjunctival inflammation.

摘要

目的

研究粉防己碱对体外培养的人结膜下成纤维细胞(SCFs)活化的影响。

方法

在SCF培养物中检测粉防己碱对SCF增殖、基质表达、肌成纤维细胞生成和细胞迁移的影响。检测粉防己碱对TGFβ1/Smad2信号和Smad7表达的影响。通过单层细胞培养中的体外缺损闭合评估迁移情况。采用蛋白质免疫印迹法和免疫细胞化学法。

结果

粉防己碱抑制伤口诱导的细胞迁移(缺损闭合)和肌成纤维细胞生成,但不抑制SCF培养物中的细胞增殖。它还降低了纤连蛋白、I型胶原和α平滑肌肌动蛋白的表达。添加粉防己碱可增加Smad7蛋白水平并抑制Smad2信号。

结论

粉防己碱通过上调Smad7抑制SCFs中的Smad2信号和纤维化反应,提示其在预防小梁切除术后结膜过度瘢痕形成/纤维化或重症结膜炎症患者中的潜在治疗价值。

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