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新型基质再生剂 (RGTA、CACICOL20) 可刺激碱烧伤角膜愈合:该生物聚合物可模拟肝素硫酸盐,减少蛋白水解、氧化和硝化损伤。

The healing of alkali-injured cornea is stimulated by a novel matrix regenerating agent (RGTA, CACICOL20): a biopolymer mimicking heparan sulfates reducing proteolytic, oxidative and nitrosative damage.

机构信息

Institute of Experimental Medicine, Center of Excellence, Academy of Sciences of the Czech Republic, Prague, Czech Republic.

Laboratoires Thea, Clermont-Ferrand, France.

出版信息

Histol Histopathol. 2014 Apr;29(4):457-78. doi: 10.14670/HH-29.10.457. Epub 2013 Oct 9.

Abstract

The efficacy of a chemically modified dextran - heparan sulfate mimicking regenerating agent (RGTA) on the healing of the rabbit cornea injured with alkali was examined. The eyes were injured with 0.15 N NaOH applied on the cornea or with 1.0 N NaOH using a 8 mm diameter filter paper disk. Then RGTA or placebo was applied on the cornea. In the last group of rabbits, corneas injured with the high alkali concentration were left without any treatment for four weeks; subsequently, the corneas were treated with RGTA or placebo. The central corneal thickness was measured using a pachymeter. The corneas were examined morphologically, immunohistochemically and for real time-PCR. Compared to control (unaffected) corneas, following the application of low alkali concentration the expression of urokinase-type plasminogen activator, metalloproteinase 9, nitric oxide synthase and xanthine oxidase was increased in the injured corneal epithelium of placebo-treated eyes, whereas the expression of antioxidant enzymes was reduced. Nitrotyrosine and malondialdehyde stainings appeared in the corneal epithelium. RGTA application suppressed the antioxidant/prooxidant imbalance and reduced the expression of the above-mentioned immunohistochemical markers. The corneal thickness increased after alkali injury, decreased during corneal healing after RGTA treatment faster than after placebo application. Following the injury with the high alkali concentration, corneal inflammation and neovascularization were highly pronounced in placebo-treated corneas, whereas in RGTA-treated corneas they were significantly supressed. When RGTA or placebo application was started later after alkali injury and corneas were ulcerated, subsequent RGTA treatment healed the majority of them. In conclusion, RGTA facilitates the healing of injured corneas via a reduction of proteolytic, oxidative and nitrosative damage.

摘要

我们考察了一种经过化学修饰的葡聚糖-硫酸乙酰肝素模拟再生剂(RGTA)对兔角膜碱烧伤愈合的疗效。用 0.15N NaOH 溶液或 1.0N NaOH 溶液作用于角膜,或者用 8mm 直径滤纸盘作用于角膜,制备角膜碱烧伤模型。然后将 RGTA 或赋形剂滴于角膜表面。在另一组兔子中,用高浓度 NaOH 溶液作用于角膜造成严重损伤,不做任何处理 4 周后,再给予 RGTA 或赋形剂处理。应用角膜测厚仪测量中央角膜厚度。用组织形态学、免疫组化和实时定量 PCR 方法检测角膜。与正常(未损伤)角膜相比,低浓度碱烧伤后,安慰剂处理组角膜上皮中尿激酶型纤溶酶原激活物、金属基质蛋白酶 9、一氧化氮合酶和黄嘌呤氧化酶的表达增加,而抗氧化酶的表达减少。角膜上皮出现硝基酪氨酸和丙二醛染色。RGTA 处理可抑制抗氧化/促氧化失衡,并降低上述免疫组化标志物的表达。碱烧伤后角膜厚度增加,经 RGTA 处理后角膜愈合加快,厚度下降较安慰剂处理更快。高浓度碱烧伤后,安慰剂处理组角膜炎症和新生血管形成明显,而 RGTA 处理组明显减轻。碱烧伤后开始应用 RGTA 或安慰剂,且角膜已发生溃疡时,应用 RGTA 治疗仍可使多数溃疡愈合。总之,RGTA 通过减少蛋白水解、氧化和硝化损伤,促进损伤角膜的愈合。

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