重组人角质细胞生长因子异构体抑制兔角膜基质细胞增殖分化的研究

Recombinant human keratinocyte growth factor variant for mechanical corneal injury in rabbits

目的观察重组人角质细胞生长因子异构体(recombinant human keratinocyte growth factor variant,K102)对实验性兔角膜损伤的治疗作用。方法108只家兔均在显微镜下造成板层切割损伤模型,并分成K102药物大剂量(0.5 mg/ml)、中剂量(0.25 mg/ml)、小剂量(0.125 mg/ml)治疗组、贝复舒对照组(贝复舒滴眼液治疗,2 400 AU/ml)、地塞米松对照组(地塞米松磷酸钠滴眼液治疗,0.25 mg/ml)和空白组(K102滴眼液的溶媒滴眼治疗)。通过裂隙灯观察角膜上皮下雾状浑浊(Haze)差别。于术后30、90 d处死动物取角膜行光镜及电镜检查。结果术后30、90 d,K102药物治疗的各组Haze评分及前50μm角膜基质层内平均角膜细胞数均明显低于阳性对照组及空白组(P<0.05),光镜及电镜检查结果显示K102大剂量组角膜成纤维细胞活化及增殖程度明显轻于贝复舒对照组、空白组。结论K102滴眼液可抑制角膜损伤后的角膜基质细胞过度增殖、活化,减少早期Haze形成。

Objective To investigate the effect of recombinant human keratinocyte growth factor variant （K102） on mechanical corneal injury in rabbits. Methods Mechanical corneal injury was made in 108 rabbits surgically. K102 eye drop was given respectively at dose of 0.5, 0.25, 0. 125 mg/ml, taking Beifushu eye drops and Dexamethasone sodium phosphate eye drops as the positive control, and K102 eye drop solvent as the blank control; 4 times per day. Corneal haze was determined with slit lamp microscope and the histopathological changes were observed under light and electron microscope. Results Three months after operation, the comeal haze was less severe and the average number of corneal cells in shallow 50 μm corneal basement was less than that in Beifushu group and blank group after 0.5 mg/ml K102 treatment. The results of light and electron microscopy showed the epithelial hypertrophy, disorders of cells and collagen arrangement after 0.5 mg/ml K102 treatment were much lighter than that in Beifushu group and blank group. Conclusion Local application of K102 eye drops reduces the number of stromal keratocyte, then effectively inhibits corneal haze at early stage after mechanical corneal injury in rabbits.