GLP-1诱导的自噬对糖尿病大鼠视网膜病变的保护作用

目的 研究GLP-1通过调控mTOR信号通路诱导的自噬对糖尿病大鼠视网膜病变是否存在保护作用。 方法 建立符合要求的糖尿病视网膜病变大鼠模型,分为模型组、胰岛素组和GLP-1组,每组6只,于造模后即刻、4周、8周、12周测定大鼠空腹血糖水平,12周后处死,取视网膜组织行HE染色,免疫组化法测LC3、P53的表达,超氧化物歧化酶法测定血清氧化应激产物ROS、MDA的含量,Western blotting法测定mTOR蛋白表达。 结果 与模型组相比,胰岛素组和GLP-1组可以明显降低空腹血糖,差异有统计学意义,而两组内比较差异无统计学意义。HE染色显示模型组视网膜神经节细胞排列紊乱,细胞减少或缺失,而胰岛素组和GLP-1组视网膜神经节细胞排列较规整,数量无明显减少,接近正常。免疫组化显示GLP-1组LC3、P53蛋白表达较其他组升高分别为(2.34±0.13,0.46±0.03),与各组比较差异均有统计学意义(P<0.05)。GLP-1组氧化应激产物ROS、MDA含量分别为(74.68±4.08,55.60±1.50),较其他组减少,各组间比较差异均有统计学意义(P<0.05)。Western blotting法测定GLP-1组mTOR蛋白含量下降(0.43±0.04),与各组间比较差异有统计学意义(F=105.447,P<0.05)。 结论 GLP-1可能通过调控mTOR信号通路,激活自噬,减少视网膜氧化应激损伤,从而达到保护视网膜的作用。

GLP-1 protected the diabetic retinopathy through induction of autophagy in rats

Objective Research the GLP-1 induced autophagy through regulation of mTOR signaling pathways, whether there is a protective role in diabetic retinopathy rats. Methods Conform to the requirements of the diabetic retinopathy rats model, divided into model group, insulin group and GLP-1 group, each group of 6, ALL the groups were measured to realise the fasting blood glucose level in rats after 0 d,4 w, 8 w and 12 w, after 12 w killing the rats, we removed the retinal tissue for HE staining and test the expression of P53, LC3 by immunohistochemical method. Collected blood serum to detect oxidative stress product ROS and MDA content with serum superoxide dismutase(SOD)method. Detected mTOR protein expression with Western blotting method. Results Compared with model group, insulin group and GLP-1 group can obviously reduce fasting blood glucose, the difference was statistically significant, and is no statistically significant difference in the two groups. HE staining showed the retinal ganglion cells of model group disordered arrangement and the cells reduced or missed, but in insulin group and GLP-1 group, retinal ganglion cells arrangement was neat, no significant decline, close to normal. Immunohistochemical display, The LC3 and P53 protein expression respectively(2.34±0.13,0.46±0.03)in GLP-1 group increased significantly compared with other groups, and the differences were statistically significance(P<0.05). Oxidative stress product ROS and MDA content respectively(74.68±4.08,55.60±1.50)in GLP-1 group reduced, compared with other groups, the differences between groups were statistically significant(P<0.05). Compared with other groups, mTOR protein content(0.43±0.04)in GLP-1 group decreased, and the differences between groups were statistically significant(F=105.447, P<0.05). Conclusion Glp-1 may through activation of autophagy by regulating mTOR signaling pathways, then reducing oxidative stress injury of retina, as to protect the retina.