白细胞介素-1α对兔眼压的影响及其眼内毒副作用的观察

The effect of interleukin-1α on intraocular pressure in rabbit eyes and its focal side effects

目的探讨白细胞介素1α(IL1α)降眼压的有效性及安全性。方法雌性新西兰白兔35只,随机分为7组,每组5只兔。A～D组分别随机一只眼结膜下注射重组人IL1α15ng(A组),前房内注射IL1α1.5ng(B组)、15ng(C组)及40ng(D组);A～D组对侧眼相应部位注射等体积的0.1%PBS。E组随机一只眼滴用噻吗心安,对侧眼滴用人工泪液。F和G组用药方法和剂量同D组,但G组双眼用药。A～D组于用药前及用药24h后连续4d分别进行眼压测量、眼前节裂隙灯显微镜及直接检眼镜检查。E组于用药前和用药后7d进行眼压测量。F组于用药24及48h后分别行双眼房水涂片,寻找炎性细胞。G组于用药前及用药后30～40h分别行角膜内皮细胞计数和闪光视网膜电图(ERG)检查,最后行组织学检查。结果A～D组用药后眼压均低于用药前(P=0.001～0.003),其中降眼压高峰期在用药后72～96h,药效持续96h以上;C、D组高峰期的降眼压幅度均高于E组(P<0.05);除局部稍充血外,A～D组采用裂隙灯显微镜和直接检眼镜检查未见明显异常。F组双眼房水炎性细胞计数比较,差异无统计学意义(P>0.05)。G组用药前后角膜内皮细胞计数和闪光ERG检测结果比较,差异无统计学意义(P>0.05),组织切片观察未见异常。结论IL1α具有降眼压效果好、幅度大、作用持续时间长、用药安全等特点,有较好的应用前景。

Objective To investigate the efficiency of interleukin-1α on intraocular pressure reduction and its safety.Methods 35 New Zealand female rabbits were randomized into seven groups. In group-A, one eye was randomly selected to receive sub-conjunctival injection of 15 ng IL-1α, and in group B-D , one eye was injected intracamerally with IL-1α 1.5 ng, 15 ng and 40 ng respectively, and the other eye was injected intracamerally with equivalent volume of 0.1% PBS as control. In group-E, one eye was treated with 0.5% timolol eye drops and the other eye was given artificial tear. Groups F and G were treated as group D, and specifically in group-G, both eyes were given IL-1α. In group-A to D, the examination of tonometry, slit-lamp biomicroscopy and direct ophthalmoscope were taken before treatment and 24 hours after the treatment and were repeated everyday for 4 days. In group-E, tonometry was applied before treatment and 7 days after treatment. In group-F, aqueous humor of two eyes was aspirated for smear examination 24 and 48 hours after treatment, and corneal endothelium microscope and flash-ERG were done in group-G before and 30 to 40 hours after treatment, and then the eyes were enucleated for histology analysis .Results IOP of the eyes received IL-1α was decreased significantly compared with that of contralateral control eyes in group A to D (P<0.05). Peaking time of IOP reduction was 72-96 hours after treatment, and IOP reduction was continued for over 96 hours. The IOP reduction efficiency in group C and D was more significant than those of group E(P<0.05). No significant abnormal was found with the examinations of slit-lamp biomicroscopy, ophthalmoscope, corneal endothelium microscopy,flash-ERG,smear and histological observation,except for mild focal conjunctival congestion.Conclusion Intraocular reduction were demonstrated with IL-1α treatment,charactered by its strong hypotensive effect,long duration and safety.