姜黄素对氧诱导的视网膜新生血管形成的影响

目的 观察姜黄素对高氧诱导视网膜病变(OIR)动物模型新生血管形成的影响.方法 C57BL/6J小鼠72只,分为正常组、OIR模型组、二甲基亚砜(DMSO)组及100、50、10 mg姜黄素治疗组.正常组小鼠饲养于正常空气的氧浓度中,其余各组小鼠参照文献建立OIR模型.治疗组在建立OIR模型后分别腹腔注射100,50、10 mg/kg姜黄素0.1 ml,DMSO组腹腔注射1‰的DMSO 0.1 ml.所有小鼠于17日龄处死,摘除眼球,苏木精-伊红染色观察并计数突破视网膜内界膜的血管内皮细胞核的数目.取各组小鼠视网膜组织,逆转录-聚合酶链式反应(RT-PCR)及蛋白质免疫印迹(Western blot)方法检测血管内皮生长因子(VEGF)-A、VEGF受体-2(VEGFR-2)、内皮抑素(ES)、磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)在视网膜中的表达.结果 与正常组比较,OIR模型组小鼠视网膜有大量新生血管形成,突破内界膜的内皮细胞核数,OIR模型组为(46.00±16.00)个,正常组为(0.17±0.41)个,差异有统计学意义(P<0.05).RT-PCR及Western blot检测显示100 nag治疗组与其余两个剂量的治疗组相比在对VEGFA、ES、p-p38MAPR表达的影响上具有更为显著的作用(P<0.05),但不同剂量治疗组之间VEGFR-2的表达,差异无统计学意义(P>0.05).结论 姜黄素能够显著抑制氧诱导视网膜新生血管的生成.

Effects of curcumin on the oxygen-induced retinal neovasularization

Objective To investigate the effects and mechanism of cureumin on the retinal neovasularization in mice with oxygen-induced retinopathy (OIR). Methods A total of 72 C57BL/6J mice were divided into normal, OIR model, vehicle control dimethyl sulphoxide (DMSO)], and curcumin group(100, 50, and 10 mg). The mice in normal group lived in normoxia condition; OIR model was set up according to standard methods in the literature. Five days after OIR establishment, the mice in curcumin group received an intraperitoneal (IP) injection of 0.1 ml curcumin (100, 50, and 10 mg), and the mice in DMSO group received an IP injection of 0. 1 ml 1‰ DMSO. All of the mice were executed at the age of postnatal day 17 (P17) and the eyeballs were collected. Endothelial cell nuclei breaking through the internal limiting membrane were counted after stained with hematoxylin and eosin (HE). The expression of vascular endothelial growth factor-A (VEGF-A), vascular endothelial growth factor receptor-2 (VEGFR-2),endostatin (ES), and phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK) in the retina in each group were measured by real-time polymerase chain reaction (RT-PCR) and Western blot methods.Results Compared with the normal group, retinal neovascularization was found in OIR model group (P<0. 05). The number of endothelial cell nuclei was 46.00 ± 16. 00 in OIR model group and 0. 17 ± 0.41 in normal group (P<0. 05). The expression of VEGF-A, ES, and p-p38MAPK in 100 nag curcumin group differed statistically from which in 50 and 10 mg curcumin group (P<0. 05). The expression of VEGFR-2 was same in the three curcumin groups (P>0. 05). Conclusion Curcumin can inhibit the formation of retinal neovascularization; the mechanism may be associated with inhibiting the expression of VEGFA and VEGFR-2, increasing the expression of ES, and inhibiting the p38MAPK signal transduction pathway.