Authors: Li Jingwen, Li Guowen, Lu Jun, Li Chunxia
Abstract [Download PDF] [Read Full Text]
Background
The pathogenesis of diabetic retinopathy (DR) involves a variety of biological pathways.Recently, inflammation factor has been thought to paly an important role in the pathogenesis of DR.Studies show that the concent of tumor necrosis factor-α (TNF-α) is increased in high-glucose environment, which leads to the abnormality of tight junction protein and follows by blood-retinal barrier (BRB) damage.Polysaccharides of dendrobium candidum (PDC) can inhibit the overexpression of TNF-α, but its effect on TNF-α in early DR procedure has been unelucidated.
Objective
This study was to investigate the effects of PDC on permeability of BRB and its mechanism in daibetic rats.
Methods
Fifty clear adult SD rats were divided into normal control group, diabetic model group and low- (100 mg/[kg·d]), moderate- (200 mg/[kg·d]) and high-dose (300 mg/[kg·d]) PDC groups, 10 rats for each group.Streptozotocin was intraperitoneally injected to establish diabetic model in 40 rats, expect for normal control group.PDC at the concentrations of 100, 200 and 300 mg/(kg·d) was intragastrically administered in the low-, moderate- and high-dose groups respectively at 6 weeks after modeling, and normal saline solution was used at the same way in the normal control group and diabetic model group.Evans blue was perfused via cardic chamber and eyes were obtained.Evants blue leakage was measured to evaluate the BRB permeability.The relative expressions of TNF-α, zonula occludens-1 (ZO-1), occludin and claudin-5 proteins were detected by Western blot; TNF-α contents in the retina and serum of the rats were detected by ELISA.
Results
The leakage concents of Evans blue in the retinas were (12.68±1.30), (30.45±2.60), (22.12±1.15), (17.99±1.00) and (21.49±1.00) in the normal control group, diabetic model goup and low-, moderate- and high-dose PDC groups, respectively, and the retinal leakage concents in the diabetic model group were significantly higher than those in the normal control group, and the retinal leakage contents in the low-, moderate- and high-dose PDC groups were lower than those in the diabetic model group (all at P<0.01). Western blot showed that the relative expression level of retinal TNF-α was significantly higher in the diabetic model group compared with the normal control group(1.12±0.10 vs.0.27±0.03), and that in the diabetic model group was significantly higher than that in the normal control group; while the relative expression levels of retinal TNF-α in different doses PDC groups were significantly lower, and the relative expression levels of retinal ZO-1, occludin and claudin-5 were significantly higher than those in the diabetic model group (all at P<0.05). ELISA showed that the concentrations of retinal and serum TNF-α were higher in the diabetic model group compared with the normal control group, and those in the different doses of PDC groups were lower than those in the diabetic model group (all at P<0.05). No significant differences were found among various doses of PDC groups (all at P>0.05).
Conclusions
PDC can improve the permeability of BRB by down-regulating the expression of TNF-α and up-regulating the expressions of tight junction proteins in the retina of diabetic rats, which is probably related to suppressing the development of early DR.