METHODS: Totally 40 C57BL/6 male mice were randomly divided into the normal group, diabetes group, siRNA-HIF-1α group and siRNA-NC group. The diabetic models were constructed. The histopathological change of the retina of the mice was observed in each group. The microvessel density(MVD)was detected by immunohistochemistry. The expressions of HIF-1α, VEGF,NF-κB, IL-1, IL-6 and TNF-α mRNA in the retina in each group were detected by real-time quantitative PCR. The expressions of HIF-1α, ET-1 and vWF proteins in the retina in each group were detected by Western blot.

RESULTS: The body weights of diabetes group, siRNA-NC group and siRNA-HIF-1α group were lower than the normal group, while the blood glucose levels were higher than the normal group(All P<0.05). The MVD in the diabetic group and siRNA-NC group were significantly higher than those in the normal group, while the siRNA-HIF-1α group were significantly lower than the diabetes group and siRNA-NC group(All P<0.05). Compared with the diabetes group and siRNA-NC group, the relative expression levels of HIF-1α, VEGF, NF-κB, IL-1, IL-6 and TNF-α mRNA in the retina in the siRNA-HIF-1α group were decreased(All P<0.05). Compared with the diabetes group and siRNA-NC group, the relative expression levels of HIF-1α,ET-1 and vWF proteins in the retina in the siRNA-HIF-1α group were decreased(All P<0.05).

CONCLUSION: Specific silencing of HIF-1α gene could protect the retina of DR. The mechanism may be related to the reduction of angiogenesis and vascular endothelial injury.