Gong Yan, Wu Guo-Hai, Zhang Ling-Yi, Zhang Zhe, Liao Yan-Hong, Liu Xiao-Tian
Department of Ophthalmology, Ningbo Eye Hospital, Ningbo 315040, Zhejiang Province, China.
Int J Ophthalmol. 2020 Jun 18;13(6):879-885. doi: 10.18240/ijo.2020.06.04. eCollection 2020.
To investigate the effects of nintedanib thermo-sensitive hydrogel (NTH) on neovascularization and related markers in corneal alkali burns of Wistar rats.
NTH was prepared by grinding, and its phase-transition temperature was determined. Thirty specific-pathogen-free Wistar rats served as a model of corneal alkali burn in the right eye were randomly divided into 3 groups (=10, each): model group treated with 0.9% saline once a day, NTH group with 0.2% nintedanib , and dexamethasone group with dexamethasone ointment once a day. The left eye of rats served as the controls. The corneal transparency was observed under a slit-lamp microscope, and the area of neovascularization was calculated. On day 7, the rats were sacrificed, and the cornea was removed and embedded with paraffin, then stained with hematoxylin-eosin, and the expression of vascular endothelial growth factor receptor 2 (VEGFR-2) and CD31 in the corneal tissues of each group was detected by immunofluorescence.
The phase-transition temperature of nintedanib obtained by grinding was 37°C after adding artificial tears. The results of the alkali burn model indicated that the growth rate of neovascularization in the NTH group was slower than that in the model group, and the neovascularization area was significantly smaller than that in the model group (<0.05). Moreover, CD31 and VEGFR-2 expression levels in the NTH group were significantly lower than those in the model group.
NTH becomes colloidal at body temperature, which is beneficial for releasing the drug slowly and can significantly inhibit the neovascularization of corneal induced by alkali burn in rats.
探讨尼达尼布热敏水凝胶(NTH)对Wistar大鼠角膜碱烧伤新生血管形成及相关标志物的影响。
研磨制备NTH,并测定其相变温度。30只无特定病原体的Wistar大鼠右眼作为角膜碱烧伤模型,随机分为3组(每组n = 10):模型组每天用0.9%生理盐水处理一次;NTH组用0.2%尼达尼布处理;地塞米松组每天用地塞米松眼膏处理一次。大鼠左眼作为对照。在裂隙灯显微镜下观察角膜透明度,并计算新生血管面积。第7天处死大鼠,取出角膜并用石蜡包埋,然后进行苏木精-伊红染色,通过免疫荧光检测每组角膜组织中血管内皮生长因子受体2(VEGFR-2)和CD31的表达。
研磨得到的尼达尼布加入人工泪液后的相变温度为37℃。碱烧伤模型结果表明,NTH组新生血管生长速度慢于模型组,新生血管面积显著小于模型组(P < 0.05)。此外,NTH组CD31和VEGFR-2表达水平显著低于模型组。
NTH在体温下变成胶体,有利于药物缓慢释放,可显著抑制大鼠碱烧伤诱导的角膜新生血管形成。