Objective: To explore the inhibiting effect of rapamycin (RAPA) on corneal neovascularization (CNV) of rats and the functional mechanism.
Methods: A design group was adopted. 102 Wistar rats were divided into four groups at random, including rapamycin liposome treated group (24 rats), the rapamycin solved in bean oil treated group (24 rats), blank liposome treated group (24 rats), blank treated group (24 rats) and normal control group (6 rats). All right eyes of 96 rats were induced by alkali cauterization. Rapamycin liposome were prepared by thin film hydration and the major factors were studied by the method of orthogonal design. After alkali burn, cauterized rats were observed by slitlamp biomicroscope every day. On the 1st, 4th, 7th, 14th days after operation, the expression of HIF-1alpha and VEGF were examined by immunohistochemical method and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). The analysis of variance and q test groups for analysis were adopted to analyze the results.
Results: (1) The bodies of RAPA liposome were intact kinds of spheres, the average diameter was 145.2 nm, and the envelopment rate was 90.02%. (2) After the burn of 14 d, CNV area of B, C, D and E group were (28.289 +/- 0.703), (28.005 +/- 0.801), (20.002 +/- 1.005) and (22.300 +/- 0.853) mm(2) (F = 159.62, P < 0.05). The CNV of both the rapamycin liposome treated group and the rapamycin solved in bean oil group grew slowly and smaller than that of blank liposome treated group and blank treated group (q = 47.80, 46.20, 34.60, 32.90;P = 0.00). While the rapamycin liposome treated group changed more obviously than the rapamycin solved in bean oil group (q = 13.20, P = 0.00). After alkali burn, the expression of HIF-1alpha and VEGF increased dramatically, meanwhile the expression of HIF-1alpha and VEGF were significantly decreased by RAPA.
Conclusions: Liposome body is an excellent medicine carrier for the RAPA. RAPA can obviously suppress the growth of CNV. The possibly mechanism is weakening VEGF expression by inhibiting the transcription factor HIF-1alpha.