Abstract: ［Abstract］ Objective〖HTSS〗〓To identify the effect of eicosapentaenoic acid (EPA) on expression of vascular endothelial growth factor(VEGF)、 flk1、bax、bcl2 in retinas of diabetic rats and to elucidate the mechanism of EPA on diabetic retinopathy(DR) treatment.
〖HTH〗〖WTHZ〗Methods〖HTSS〗〓Thirtysix diabetic models of SD rats were prepared by intraperitoneal injection of streptozotocin(STZ) 60 mg/kg. One month later the rats were divided into 4 groups randomly. C：12 rats were received intravitreal injection of VEGF(0.05 μg) both eyes. D：12 rats were received intravitreal injection of VEGF(0.05 μg) and EPA（0.5 μg） both eyes. E：8 rats were received intravitreal injection of VEGF(0.05 μg) both eyes，and 2 weeks later received intravitreal injection of EPA（0.5 μg） both eyes. F：4 rats were received intravitreal injection of VEGF(0.05 μg) both eyes，and 4 weeks later received intravitreal injection of EPA（0.5 μg） both eyes. Using complete random design empirical method，we observed the variation of VEGF、flk1、bax、bcl2 expression in diabetic rat retina established by symphysial injection and those treated by EPA by immunohistochemistry and measured the average optical density value of them in retinal ganglion cell layer and inner plexiform layer by MIAS 1998 type image analysis system.
〖HTH〗〖WTHZ〗Results〖HTSS〗〓VEGF 、flk1 expression was weakened in inner retina layer after EPA injection during background stage and preproliferation stage. But it is ineffective as given EPA during proliferation stage. EPA can weaken expression of bax in retinas and then inhibit advancement of DR after injection intravitreously. Therapeutic efficacy was better as given during background and preproliferation stage than during proliferation stage. EPA can weaken the higher expression of bcl2 in retinas by inhibiting advancement of DR, as time went to 8 weeks, the weakening effect disappeared and bcl2 continued to protect the nerve cells.
〖HTH〗〖WTHZ〗Conclusion〖HTSS〗〓EPA can inhibit advancement of DR not only  by suppressing VEGF effect through blocking flk1 receptor as given during background and preproliferation stages in vivo, but also by inhibiting apoptosis of retinal nerve cells through downregulating apoptosis trigger gene bax expression. At early stage, it can lessen compensatory higher bcl2 expression. At 8 weeks, this effect disappeared and bax/bcl2 ratio was decreased，which had the protection to pericyte deficiency.

Key words: diabetic retinopathy, vascular endothelial growth factor, eicosapentaenoic acid