Xie Mao-Song, Zheng Yong-Zheng, Huang Li-Bin, Xu Guo-Xing
Department of Ophthalmology, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China.
Department of Ophthalmology, Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou 350005, Fujian Province, China.
Int J Ophthalmol. 2017 Dec 18;10(12):1824-1829. doi: 10.18240/ijo.2017.12.06. eCollection 2017.
To clarify the mechanism of infliximab treatment in diabetic macular edema (DME) and to provide a new alternative therapy for DME.
Rats were randomly divided into the control group, the model group and the infliximab treatment group. A diabetic rat model was created. The concentration of TNF-α in the vitreous body was detected by ELISA. The expressions of B-Raf, p38, claudin-1 and occludin in the retina were detected by Western blot. The integrity of the blood retinal barrier (BRB) was measured using Evan's blue as a tracer.
After three months and six months of the diabetes model, the vitreous TNF-α level in the model group was higher than that of the control group. It was also higher in treated group than that of the control group but was lower than that of the model group. The differences among the three groups were statistically significant (at 3mo, =857.098, <0.001; 6mo, =1261.897, <0.001). The retina B-Raf and p38 levels in the model group were higher than that of the control group. They were also higher in treated group than that of the control group but were lower than that of the model group. The differences among the three groups were statistically significant (B-Raf at 3mo, =106.596, <0.001 and at 6mo, =200.681, <0.001; p38 at 3mo, =41.662, <0.001 and at 6mo, =67.979, <0.001). The retina claudin-1 and occludin levels in the model group were lower than that of the control group. They were also lower in treated group than that of the control group but were higher than that of the model group. The differences among three groups were statistically significant (claudin-1 at 3mo, =139.088, <0.001 and at 6mo, =128.415, <0.001; occludin at 3mo, =92.733, <0.001 and at 6mo, =104.478, <0.001). The retinal Evans blue leakage in the model group was higher than that of the control group. It was also higher in treated group than that of the control group but was lower than that of the model group. The differences among the three groups were statistically significant (at 3mo, =447.946, <0.001; at 6mo, =1610.732, <0.001).
In a diabetic rat model, infliximab may relieve TNF-α induced BRB breakdown the B-Raf and p38 signaling pathway.
阐明英夫利昔单抗治疗糖尿病性黄斑水肿（DME）的机制，并为DME提供一种新的替代疗法。
将大鼠随机分为对照组、模型组和英夫利昔单抗治疗组。建立糖尿病大鼠模型。采用酶联免疫吸附测定法（ELISA）检测玻璃体中肿瘤坏死因子-α（TNF-α）的浓度。采用蛋白质免疫印迹法检测视网膜中B-Raf、p38、紧密连接蛋白-1（claudin-1）和闭合蛋白（occludin）的表达。以伊文思蓝作为示踪剂，检测血视网膜屏障（BRB）的完整性。
糖尿病模型建立3个月和6个月后，模型组玻璃体TNF-α水平高于对照组。治疗组玻璃体TNF-α水平也高于对照组，但低于模型组。三组间差异具有统计学意义（3个月时，F = 857.098，P < 0.001；6个月时，F = 1261.897，P < 0.001）。模型组视网膜B-Raf和p38水平高于对照组。治疗组视网膜B-Raf和p38水平也高于对照组，但低于模型组。三组间差异具有统计学意义（B-Raf在3个月时，F = 106.596，P < 0.001；6个月时，F = 200.681，P < 0.001；p38在3个月时，F = 41.662，P < 0.001；6个月时，F = 67.979，P < 0.001）。模型组视网膜claudin-1和occludin水平低于对照组。治疗组视网膜claudin-1和occludin水平也低于对照组，但高于模型组。三组间差异具有统计学意义（claudin-1在3个月时，F = 139.088，P < 0.001；6个月时，F = 128.415，P < 0.001；occludin在3个月时，F = 92.733，P < 0.001；6个月时，F = 104.478，P < 0.001）。模型组视网膜伊文思蓝渗漏高于对照组。治疗组视网膜伊文思蓝渗漏也高于对照组，但低于模型组。三组间差异具有统计学意义（3个月时，F = 447.946，P < 0.001；6个月时，F = 1610.732，P < 0.001）。
在糖尿病大鼠模型中，英夫利昔单抗可能通过B-Raf和p38信号通路减轻TNF-α诱导的BRB破坏。
