外伤性兔眼内炎房水中肿瘤坏死因子-α、白细胞介素-1β及中性粒细胞趋化因子-1的相对含量变化及意义

Changes of tumor necrosis factor-α,interleukin-1β and cytokine induced neutrophil chemoattractant-1 in aqueous humor of rabbits with traumatic endophthalmitis

目的通过分析兔眼外伤后不同时间点房水中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)、中性粒细胞趋化因子-1(cytokine induced neutrophil chemoattractant-1,CINC-1)含量的动态变化,探讨促炎细胞因子在外伤性眼内炎中的作用机制。方法将18只兔随机分为3组,每组6只,其中Ⅰ组为正常对照组,Ⅱ组为无菌外伤组,Ⅲ组为有菌(金黄色葡萄球菌)外伤组。Ⅱ组和Ⅲ组兔右眼建立外伤性眼内炎模型,并将金黄色葡萄球菌接种于Ⅲ组兔右眼的玻璃体内。于造模后6h、12h、1d、2d、4d、5d、7d、14d用裂隙灯及间接检眼镜观察眼部炎症情况并进行临床炎症评分。ELISA法测定各组造模后6h、12h、1d、2d、4d、5d房水中TNF-α、IL-1β、CINC-1的含量变化。结果造模后12h、1d、2d、4d、5d、7d、14d,Ⅱ组各时间点临床炎症评分分别为(2.50±0.55)分、(3.67±0.82)分、(4.00±0.63)分、(6.12±0.75)分、(7.00±0.63)分、(7.33±0.52)分、(5.50±0.54)分,Ⅲ组分别为(4.00±0.63)分、(6.17±0.75)分、(7.67±0.52)分、(10.60±0.82)分、(11.50±0.55)分、(11.80±0.41)分、(10.33±0.51)分,两组各时间点临床炎症评分间差异均有统计学意义(均为P<0.05),造模12h后Ⅲ组炎症反应明显较Ⅱ组重。Ⅱ组和Ⅲ组兔房水中TNF-α在炎症初期就开始升高,1d时达到高峰,与Ⅰ组相比差异均有统计学意义(均为P<0.05)。Ⅱ组和Ⅲ组兔房水中IL-1β含量于造模后1d时达到高峰,与Ⅰ组相比差异均有统计学意义(均为P<0.05)。Ⅱ组和Ⅲ组兔房水中CINC-1含量在造模后12h时即达到高峰,与Ⅰ组相比差异均有统计学意义(均为P<0.05)。Ⅱ组和Ⅲ组兔房水中TNF-α、IL-1β、CINC-1各时间点相比差异均无统计学意义(均为P>0.05)。结论外伤后机体的免疫调节机制在外伤性眼内炎发生发展过程中发挥重要作用,房水中TNF-α、IL-1β、CINC-1表达升高与炎症程度相关,调控细胞因子网络可能成为未来眼内炎一个有效的联合治疗措施。

Objective To investigate the mechanism of pro-inflammatory cyto- kines of rabbits with traumatic endophthalmitis by analyzing dynamic changes of related contents of tumor necrosis factor-α （ TNF-α ）, interleukin-1β（ IL-1β ） and cytokine in- duced neutrophil chemoattractant-1 （ CINC-1 ） in their aqueous humors. Methods A total of 18 rabbits were divided into three groups,5 rabbits in each group. Group I was the normal group ,and the animal models of traumatic endophthalnu＇tis were established in rabbits of group lI （asepsis） and Ⅲ（ staphylococcus aureus ）. And staphylococcus aureus were injected into the vitreous cavity of traumatic eyes in group Ⅲ Clinical ob- servation was done at 6 hours,12 hours,1 day,2 days,4 days,5 days,7 days,and 14 days after modeling by slit lamp and indirect ophthalmofundoscope and evaluated with clini- cal grading system. ELISA assay was applied to detect the content changes of TNF-a,IL-1β,CINC-1 in the aqueous humor before modeling and at 6 hours, 12 hours, 1 day,2 days,4 days, and 5 days after modeling. Results At 12 hours, 1 day, 2 days,4 days, 5 days,7 days and 14 days after modeling, the clinical inflammation scores at different points in group ]I were （2.50 ± 0.55 ） scores, （ 3.57 ± 0.82） scores, （4.00 ± 0.63 ） scores, （6. 12±0.75） scores, （7.00±0. 63） scores, （7.33 ±0. 52） scores and（5.50 ±0.54） scores,and group m were（4.00 ±0.63） scores, （6. 17 ±0.75） scores, （7.57 ±0. 52） scores, （ 10.60 ± 0. 82） scores, （ 11.50 ± 0.55 ） scores, （11. 80 ± 0.41 ） scores and （ 10.33 ± 0.51 ） scores. There were statistical differences in clinical scores at each time point be- tween group ]I and group ]][ （ all P 〈 0. 05 ）, Inflammatory reaction in group Ⅲ was markedly heavier than that in group Ⅱ. The levels of TNF--α in the aqueous humor after modeling in group Ⅱ and Ⅲ all increased from the beginning,increased clearly at 12 hours,peaked at 1 day, and compared with group Ⅰ , there were statistical differences （ all P 〈 0.05 ）. The levels of IL-1β in the aqueous humor after modeling in group Ⅱ and Ⅲ peaked at 1 day, and compared with group I , there was statistical difference （both P 〈 0.05 ）. The levels of CINC-1 in the aqueous humor after modeling in group Ⅱ and Ⅲpeaked at 12 hours, and compared with group , there was statistical difference（ both P 〈 0.05 ）. Conclusion Post-traumatic immune regulation mechanism plays an important role in the development of traumatic endophthalmitis, high expression levels of TNF-α,IL-1β and CINC-1 in aqueous humors are associated with the degree of inflam-mation. The regulation of cytokine network may become an effective combination therapy of endophthalmitis in the future.