目的：探讨小分子RNA干扰HIF-1α对糖尿病视网膜病变小鼠视网膜的保护作用及机制。

方法：C57BL/6雄性小鼠40只随机分为正常组、糖尿病组、siRNA-HIF-1α组、siRNA-NC组，制备糖尿病模型。观察各组小鼠视网膜组织病理学变化，免疫组织化学检测微血管密度(MVD)，实时荧光定量PCR检测各组小鼠视网膜组织中HIF-1α、VEGF、NF-κB、IL-1、IL-6、TNF-α mRNA表达，Western blot法检测各组小鼠视网膜组织中HIF-1α、ET-1、vWF蛋白表达。

结果：糖尿病组、siRNA-NC组和siRNA-HIF-1α组大鼠的体质量低于正常组，而血糖水平高于正常组(均P<0.05)； 糖尿病组和siRNA-NC组小鼠视网膜组织中MVD高于正常组，而siRNA-HIF-1α组低于糖尿病组和siRNA-NC组(均P<0.05)； 与糖尿病组和siRNA-NC组相比，siRNA-HIF-1α组小鼠视网膜组织中HIF-1α、VEGF、NF-κB、IL-1、IL-6、TNF-α mRNA相对表达量降低(均P<0.05)； 与糖尿病组和siRNA-NC组相比，siRNA-HIF-1α组小鼠视网膜组织中HIF-1α、ET-1、vWF蛋白相对表达量降低(均P<0.05)。

结论：特异性沉默HIF-1α基因可保护DR小鼠视网膜，其机制可能通过减少血管新生和血管内皮损伤有关。

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.