Losartan Attenuates Scar Formation in Filtering Bleb After Trabeculectomy
Losartan Attenuates Scar Formation in Filtering Bleb After Trabeculectomy
复制标题
氯沙坦可减轻小梁切除术后滤过泡的疤痕形成
DOI：
10.1167/iovs.16-21163
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发表时间：
2017-03-01
影响因子：
4.4
通讯作者：
Ye, Wen
中科院分区：
文献类型：
--
作者：
Shi, Huimin;Wang, Huiying;Ye, Wen
目的。检查小梁切除术后氯沙坦对疤痕形成的影响，以及人田not骨成纤维细胞（HTFS）的纤维化变化。小梁切除术是在新西兰兔子上进行的。它们被随机接受以下治疗方法之一：0.9％的正常盐水，丝裂霉素-C或三种氯沙坦剂量之一。进行了BLEB形态，IOP和组织病理学检查。原代培养的HTF用Losartan或载体处理，有或没有血管紧张素II（ANG II）。通过细胞计数KIT-8测定法评估细胞增殖，并通过刮擦伤口和Transwell分析检测细胞迁移。通过免疫荧光，实时PCR和Western blot的表达来评估跨分化。纤连蛋白（FN）的表达通过实时PCR和Western blot.Results评估。在兔模型中，术后IOP量5 mg/ml losartan副结膜注射可显着降低IOP，并减弱过滤BLEB的伤口愈合。免疫染色的结果显示，在莱萨坦治疗的眼睛中，周围的BLEB区域周围的肌纤维细胞和胶原蛋白沉积较少。 Losartan（10（-5）M）体外显着减弱了Ang II对HTF的增殖和迁移的刺激作用。这些细胞中A-SMA和FN的表达也通过Losartan预处理降低。小梁切除术后液体形成滤波器的疤痕形成可能是通过降低鼻孔成纤维细胞的增殖，迁移，转分化和细胞外基质沉积的可能性来减少疤痕。这些结果表明，氯沙坦可能是防止疤痕形成和提高小梁切除术后手术结局的有效治疗剂。
PURPOSE. To examine the effects of losartan on scar formation after trabeculectomy and on fibrotic changes of human Tenon's fibroblasts (HTFs).METHODS. Trabeculectomy was performed on New Zealand rabbits. They were randomized to receive one of the following treatments: 0.9% normal saline, mitomycin-C, or one of the three doses of losartan. Bleb morphology, IOP, and histopathology examination were performed. Primary cultured HTFs were treated with losartan or vehicle, with or without angiotensin II (Ang II). Cell proliferation was assessed by Cell Counting Kit-8 assay, and cell migration was detected by scratch wound and transwell assay. Transdifferentiation was evaluated through the expression of a-smooth muscle actin (alpha-SMA) by immunofluorescence, real-time PCR, and Western blot. The expression of fibronectin (FN) was evaluated by real-time PCR and Western blot.RESULTS. An amount of 5 mg/mL of losartan subconjunctival injection significantly decreased IOP postoperatively and attenuated wound healing of the filtering bleb in the rabbit model. Immunostaining results showed less myofibroblast and collagen deposition around the bleb area in the losartan-treated eyes. Losartan (10(-5) M) in vitro significantly attenuated Ang II's stimulatory effects on proliferation and migration of HTFs. Expressions of a-SMA and FN in these cells were also decreased by losartan pretreatment.CONCLUSIONS. Losartan attenuates scar formation of filtering bleb after trabeculectomy likely via decreasing proliferation, migration, transdifferentiation, and extracellular matrix deposition of Tenon's fibroblasts. These results indicate that losartan may be an effective therapeutic agent in preventing bleb scar formation and in improving surgical outcome after trabeculectomy.