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Objective
To observe the effect of recombinant human vascular endostatin(ES) on retinal barrier related proteins in early streptozotocin (STZ)-induced diabetic rats.
Methods
Diabetes rat model was induced by STZ.Two weeks after the model was successfully constructed, 36 diabetic model rats were randomly divided into the model group, 1.0 μl ES group, 2.5 μl ES group, 5.0 μl ES group, 2.5 μl bevacizumab group, and the combination therapy group, with 6 rats in each group.Different doses of recombinant human ES and 2.5 μl bevacizumab were injected into the vitreous cavity of the right eye according to the grouping.Six normal rats were selected as the blank control group.At 4 weeks after intravitreal injection, the retinal tissue of the right eye in each group was collected, and the expression levels of inter cellular cell adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), occludin, claudin-5, vascular endothelial growth factor(VEGF) and other proteins in retinal tissue were detected by Western blot assay.The use and care of animals was in accordance with the regulations for the administration of experimental animals.
Results
The diabetic model rats showed polydipsia, polyuria, polyphagia and other typical diabetic symptoms, the body quality decreased significantly, and the success rate of modeling was 100%.Western blot results showed that the expression levels of VCAM-1, ICAM-1 and VEGF in the blank group, the 2.5 μl ES group, the 5.0 μl ES group, the bevacizumab group, the combination therapy group were significantly lower than those in the model group, while the expression levels of claudin-5 and occludin were significantly higher than those in the model group, the differences were statistically significant (all at P<0.05). The relative expression of occludin protein in the 1.0 μl ES group was significantly higher than that in the model group(0.23±0.02 vs.0.13±0.02), while the relative expression of ICAM-1 and VEGF was significantly lower than that in the model group(0.53±0.01 vs.0.81±0.01; 0.57±0.00 vs.0.86±0.00), the differences were statistically significant (all at P<0.05). As the dose of ES increased, the relative expressions of claudin-5 and occludin protein tended to increase, while the relative expressions of VCAM-1, ICAM-1 and VEGF tended to decrease.
Conclusions
Recombinant human vascular endostatin can directly or indirectly reduce the release of inflammatory factors VCAM-1 and ICAM-1 and inhibit the expression of VEGF, thereby reduce the loss of retinal tight junction.