非诺贝特对实验性糖尿病大鼠早期视网膜病变的影响

Effects of fenofibrate on early retinopathy in rats with experimental diabetes

目的观察非诺贝特对早期糖尿病性视网膜病变(DR)大鼠视网膜组织血管内皮生长因子(VEGF)、蛋白激酶C(PKC)表达及细胞凋亡的影响,探讨非诺贝特防治早期DR的作用机制。方法将实验用封闭群4周雄性健康SD大鼠50只随机分成正常组(10只)、糖尿病组(20只)和非诺贝特组(20只)。非诺贝特组和糖尿病组均采用链脲佐菌素(STZ)一次性腹腔注射制作糖尿病模型。非诺贝特组每天给予非诺贝特10 mg/kg与饲料混合后喂养,糖尿病组与正常组给予普通饲料喂养。记录给药前及给药4,8,12,16周时3组空腹血糖水平。给药16周后处死大鼠,取眼球,制作视网膜组织切片,采用免疫组织化学染色法检测VEGF和PKC蛋白表达情况,采用原位末端脱氧核糖核苷酸转移酶标记技术(TUNEL)检测细胞凋亡情况。结果给药4,8,12,16周非诺贝特组和糖尿病组空腹血糖水平均显著高于正常组(P均<0.05),但2组间比较差异无统计学意义(P>0.05)。给药16周后3组大鼠视网膜VEGF和PKC蛋白表达水平比较差异均有统计学意义(P均<0.05),其中糖尿病组与非诺贝特组大鼠VEGF和PKC蛋白表达水平较正常组明显上调(P均<0.05),但非诺贝特组较糖尿病组明显降低(P均<0.05)。非诺贝特组及糖尿病组视网膜组织细胞凋亡指数均明显高于正常组(P均<0.05),但非诺贝特组视网膜组织细胞凋亡指数显著低于糖尿病组(P<0.05)。结论非诺贝特可下调早期糖尿病大鼠视网膜组织中VEGF和PKC表达,减少视网膜组织细胞凋亡,干预早期DR的发生发展。

Objective It is to observe the influence of fenofibrate on vascular endothelial growth factor（ VEGF） and protein kinase C（ PKC） expression and cell apoptosis in retinal tissue of rats with earlier diabetic retinopathy（ DR）,and explore the mechanism of fenofibrate for the prevention and treatment of early DR. Methods 50 male healthy Sprague-Dawley rats were randomly divided into normal control group（ 10 cases）,fenofibrate group（ 20 cases） and diabetes mellitus（ DM） group（ 20cases）. The animals in fenofibrate group and DM group were injected streptozotocin（ STZ） intraperitoneally once to set up DM model. Then the animals were fed with fenofibrate（ 10 mg / kg） and feed mixture in fenofibrate group and normal feed in DM group and normal control group. The blood-fasting glucose at the end of the 4th week,8th week,12 th week and 16 th week were detected. After 16 weeks the rats were sacrificed and retinal tissue was obtained for immunohistochemical staining to detect the expression of VEGF and PKC,the apoptosis in retina was detected by Td T- d UTP terminal nick-end labeling（ TUNEL） staining. Results The blood-fasting glucose levels of the fenofibrate group and DM group were significantly higher than that of the normal control group at the end of the 4th week,8th week,12 th week and 16 th week（ all P〈0. 05）,but there were no significant difference between the fenofibrate group and DM group（ P〈0. 05）. There were significant differences in the expressions of VEGF and PKC at the end of the 16 th week among the three groups（ all P〈0. 05）,and which were significantly higher in the fenofibrate group and DM group than those in the normal control group（ all P〈0. 05）,but that of the fenofibrate group was lower than that of the DM group（ P〈0. 05）. The apoptosis index of fenofibrate group and DM group were higher than that of the normal control group（ all P〈0. 05）,but which of the fenofibrate group was significantly lower than that of the DM group（ P〈0. 05）. Conclusion Fenofibrate can down regulate the expression of VEGF and PKC in retinal tissue of earlier DM rats and reduce the apoptosis of retinal tissue,which may interfere in the development of earlier DR.