外源性p27Kip1对兔眼滤过术后结膜瘢痕的抑制作用

目的观察外源性p27Kip1作用于兔眼滤过术后的效果,研究其对术后结膜瘢痕形成的抑制作用。方法根据GenBank人p27基因序列设计引物,制备腺病毒介导Ad-p27并验证其正确性。兔眼滤过术中结膜下注射Ad-p27、丝裂霉素C(MMC)和PBS,术后28d内测定眼压、观察眼前节的动态变化及并发症,依照Krofeld评分法进行滤过泡评分。结果 Ad-p27作用后28d内维持低眼压的状态,术后3d眼压下降达峰值7.68mmHg。Ad-p27降眼压程度与MMC相似,与PBS比较术后7d(P<0.05)、14d(P<0.01)、21d(P<0.01)和28d(P<0.05)眼压存在显著性差异。Ad-p27作用后14d内滤过泡弥漫性隆起,28d有囊性泡形成。Ad-p27组与PBS组比较,滤过泡评分在7d(P<0.01)、14d(P<0.01)和21d(P<0.05)有显著性差异。Ad-p27组术后21d前房恢复正常,而PBS组术后14d恢复正常。Ad-p27作用偶有前房渗出、前房出血等并发症。结论 Ad-p27通过抑制手术区瘢痕形成保持滤过道通畅,降低眼压。

Inhibition of scar formation in conjunctiva by exogenous p27Kip1 in a rabbit model of glaucoma filtration surgery

Objective To observe the outcome in an experimental glaucoma filtration surgery(GFS) by exogenous p27Kip1 and to investigate the postsurgical inhibition of scar formation.Methods The primer was designed according to p27 gene sequence of GenBank.Adenovirus-mediated Ad-p27 was constructed and transinfected into 293 cells;gene sequencing was performed to assess the cloning gene.Gene therapy was performed by delivery of Ad-p27 into subconjunctiva;mitomycin C(MMC) and PBS served as controls.We also observed surgical outcome and histological features,including intraocular pressure(IOP),alterations of anterior chamber,complications,and bleb score during the 28-day period.Results IOP significantly decreased in Ad-p27 group,with the maximal decrease being 7.68 mmHg on day 3 of surgery.Ad-p27 group and MMC group had similar hypotensive responses.In contrast,the PBS-induced hypotensive response was rapidly recovered on day 14.There were significant differences between Ad-p27 group and PBS group on day 7(P<0.05),14(P<0.01),21(P<0.01) and 28(P<0.05).The Ad-p27-induced filtration blebs were elevated diffusely within 14 days and cystic blebs formed on day 28.Ad-p27 group and PBS group differed significantly in filtration bleb score on day 7(P<0.01),14(P<0.01) and 21(P<0.05).The shallow anterior chamber was recovered on day 21 in Ad-p27 group,while recovered on day 14 in PBS group.There were adventitious complications,such as exudation and bleeding in anterior chamber.Conclusion Ad-p27 keeps the aqueous humor outflow by inhibiting scar formation and decreases IOP.