sgp130对糖尿病小鼠视网膜p-STAT3及VEGF-A表达的影响

Effects of soluble glycoprotein 130 on expression of p-STAT3 and vascular endothelial growth factor-A in retina of mice with diabetes mellitus

摘要:

目的：观察可溶性糖蛋白130(sgp130)对糖尿病(DM)小鼠视网膜p-STAT3及VEGF-A表达的影响，探讨sgp130防治糖尿病视网膜病变(DR)炎性损害的可能性。方法：小鼠45只被随机分为正常组、DM组和sgp130组。采用链脲佐菌素对DM组和sgp130组进行DM造模。正常组、DM组不做特殊干预，sgp130组在第1、5wk被给予1.5mg/mL sgp130 2μL进行玻璃体腔注射治疗。10wk后处死所有小鼠，检查视网膜组织IL-6、p-STAT3、VEGF-A等蛋白的表达。结果：在第10wk时，DM组视网膜IL-6、p-STAT3、VEGF-A表达较正常组升高(均P<0.01)。sgp130组p-STAT3、VEGF-A表达水平较DM组低(均P<0.01)。结论：sgp130可以选择性拮抗IL-6反式信号传导通路，下调下游炎性因子VEGF-A的表达，可以用于干预DM引起的IL-6相关性视网膜炎性损害。

Abstract:

AIM: To observe the effect of soluble glycoprotein 130(sgp130)on expression of p-STAT3 and vascular endothelial growth factor(VEGF)-A in retina of mice with diabetes mellitus(DM), and explore the possibility of sgp130 in interfering with inflammatory damage of diabetic retinopathy(DR).METHODS: A total of 45 mice were randomly divided into normal group, DM group and sgp130 group. DM models were made in DM group and sgp130 group with streptozotocin. No special intervention was given to normal group and DM group, but sgp130 group was given intravitreal injection of 1.5mg/mL sgp130 2μL at the 1 and 5wk. After 10wk, all the mice were sacrificed to assess the protein expression of interleukin 6(IL-6), p-STAT3 and VEGF-A in the retina.RESULTS: The expressions of IL-6, p-STAT3 and VEGF-A in retina of DM group were higher than those of normal group at 10wk(all P<0.01). The expression of p-STAT3 and VEGF-A in sgp130 group were lower than those in DM group(all P<0.01).CONCLUSION: The sgp130 can selectively antagonize the trans signal transduction pathway of IL-6, down-regulate the expression of downstream inflammatory factors VEGF-A, and it may be used in the intervention of retinal inflammatory damage related with IL-6 in DM.