糖尿病鼠视网膜细胞间黏附分子-1的表达与血视网膜屏障破坏的关系及曲安奈德的治疗作用

Relationship between expression of retinal intercellular adhesion molecule-1 and blood-retinal barrier rupture and therapeutic effect of triamcinolone acetonide in diabetic rats

目的探讨糖尿病(DM)鼠视网膜血管细胞间黏附分子-1(ICAM-1)在血视网膜屏障(BRB)破坏中的作用及玻璃体注射曲安奈德(TA)对BRB破坏的治疗作用。方法60只Wistar鼠建立DM模型,分为对照组、DM4个月组和DM6个月组。每组各分为免疫组织化学组和BRB测定组,BRB测定组再分为未行TA治疗组、TA治疗1周组和2周组。大鼠玻璃体内注射TA5μl。视网膜铺片免疫组织化学染色观察视网膜ICAM-1的表达及形态学变化,图像分析软件测定内皮细胞平均吸光度(A)[旧称光密度(OD)],定量ICAM-1表达。测定视网膜伊凡思蓝(EB)含量,评价BRB的变化。结果免疫组织化学组:对照组视网膜血管无明显ICAM-1阳性表达,同对照组相比,DM4个月组阳性表达显著增强(P<0.001),已出现毛细血管管径粗细不一等形态学改变;DM6个月组阳性表达进一步增强(P<0.001),形态学改变进一步加重,可出现无细胞性毛细血管。BRB测定组:各对照组间EB含量无统计学差异(P>0.05)。未行TA治疗组中,两DM组EB含量明显高于对照组(P<0.001),且DM6个月组高于4个月组(P<0.01)。TA治疗组中,各DM组EB含量均显著降低(P<0.001),但组间无统计学差异(P>0.05),然而DM4个月治疗2周组已基本恢复正常(P>0.05),余治疗组仍高于对照组(P<0.05)。内皮细胞A值与视网膜EB含量呈直线相关(r=-0.959)。结论糖尿病鼠视网膜ICAM-1的表达与BRB破坏呈正相关。玻璃体内注射TA可有效减轻BRB破坏。

Objective To investigate the relationship between expression of retinal intercellular adhesion molecule-1 （ICAM-1） and blood retinal barrier （BRB） rupture and therapeutic effect of intravitreous injection with triamcinolone acetonide （TA） on blood retinal barrier rupture in rats with diabetes mellitus （DM）. Methods Diabetic model of Wistar rats was induced and were divided into normal control group, DM-4-month group and DM-6 month group. Each group was subdivided into immunohistochemcial staining and BRB measurement groups. BRB measurement group was further divided into non TA treatment group, 1-week-TA treatment group, and 2-week TA treatment group. The rats were intravitreously injected with 5 μl TA. The digested retinal preparation was stained by immunohistochemcial method to observe the expression of retinal ICAM-1 and morphological changes. The mean optic density （A）value of endothelial cells was measured by image analyzing software to quantify the expression of ICAM-1. BRB changes were measured by content test of retinal Evans blue （EB）. Results In the immunohistochemcial staining groups, there was no significant positive expression of ICAM-1 in retinal capillary in control group. Compared with the control, there was significant positive expression of ICAM-1 in DM-4 month group （P〈0. 001） with some morphological changes such as irregular width of capillary caliber, and there was enhanced positive expression of ICAM 1 in DM-6 month group （P〈0. 001 ）with aggravated morphological changes and even acellular capillary. In the BRB measurement groups, there was no significant difference of EB content（P〉0. 05） among cont rol groups. The EB content in two DM groups significantly increased compared with that in the controls （P〈0. 001）, and higher in DM 6-month group than that in DM-4 month group （P〈0. 01）. In TA treatment groups, the EB content in all the DM groups significantly decreased （P〈0.001） but with no significant diffcrence among the groups （P〉 0. 05）. EB content in DM 4-month group after 2-week treatment almost reached to normal value （P〉0.05） while was higher in the rest of TA treatment groups than that in the control group （P〈0.05）. Rectilinear correlation between A value of endothelial cells and the retinal EB content （r= -0. 959）was found. Conclusion There is a positive relation between the expression of ICAM-1 and BRB rupture in retina of I）M rats, and intravitreous injection with TA can effectively alleviate BRB rupture.