Objective: To observe the effect of Tongxinluo on expression of hypoxia inducible factor 1a (HIF-1a)

vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) in retina tissues of KK/Upj-Ay mice with spontaneous diabetes

and explore the protective mechanism of Tongxinluo on diabetic retinopathy. Method: Forty KK/Upj-Ay mice were randomly divided into 4 groups:model group (n=10)

Tongxinluo low-dose group (n=10

1 g·kg-1)

median-dose group (n=10

2 g·kg-1) and high-dose group (n=10

4 g·kg-1) group. The mice were given Tongxinluo intragastrically for 12 weeks. C57BL/6 mice were chosen as normal group (n=10). The whole blood viscosity and plasma viscosity were measured by blood viscometer and red blood cell aggregation index was measured by ektacytometer. The expression levels of VEGF and VEGFR-2 genes in retina tissues of mice were detected with real time fluorescence quantitative PCR method. Western-blot method was used to detect the expression levels of HIF-1a

VEGF

VEGFR2 in retina tissues. Result: Compared with C57BL/6 mice in the normal group

the whole blood viscosity

the plasma viscosity and the red blood cell aggregation index were all increased in model group (P<0.01). Compared with the model group

red blood cell aggregation index was significantly decreased in KK/Upj-Ay mice after treatment by middle dose and high dose Tongxinluo (P<0.05

P<0.01)

and the whole blood viscosity at low shear rate

and plasma viscosity were also significantly decreased in high-dose Tongxinluo group (P<0.01). HIF-1a/VEGF/VEGFR-2 proteins and VEGF/VEGFR-2 mRNA expressions in retina tissues of model group mice were significantly higher than those in normal group (P<0.01)

while after treatment with Tongxinluo

HIF-1a/VEGF/VEGFR-2 mRNA and protein expressions were significantly lower in low-dose

median-dose and high-dose groups than those in model group(P<0.01). Conclusion: Tongxinluo may inhibit HIF-1a/VEGF/VEGFR-2 signal pathways in retina tissues of diabetic mice

which may be related to it's improvement of hemorrheology.