过氧化物酶增生体激活受体-γ激动剂对糖尿病大鼠血-视网膜屏障通透性的影响

目的观察过氧化物酶增生体激活受体-γ（PPAR-γ）激动剂罗格列酮对链脲佐菌素（STZ）诱导的早期糖尿病（DM）大鼠血-视网膜屏障通透性的影响。方法 90只Wistar大鼠随机分为正常对照组、DM组和DM＋罗格列酮组,每组30只。采用STZ腹腔内注射法制作DM模型。DM＋罗格列酮组造模后3d给予罗格列酮3mg/kg灌胃,每日1次,正常对照组和DM组大鼠以同样的方法给予同等剂量的DMSO灌胃。于给药后4、8、12周时处死各组大鼠各5只,进行伊凡思蓝（EB）左心室灌注后制备视网膜消化铺片并进行血-视网膜屏障通透性测定,对视网膜消化切片上视网膜血管壁的周细胞和内皮细胞进行计数,评估大鼠高血糖对视网膜毛细血管的影响。结果造模后4、8、12周,DM组和DM＋罗格列酮组大鼠的血糖水平较正常对照组明显升高,差异均有统计学意义（P〈0.01）。造模后DM组大鼠随着时间的延长,视网膜毛细血管壁周细胞减少,内皮细胞增多,毛细血管迂曲、扩张,血-视网膜屏障通透性增加（P〈0.01）,且视网膜血管的渗透值与正常对照组比较也明显增加,差异有统计学意义（P〈0.01）。DM＋罗格列酮组视网膜微血管病理损害明显减轻,血-视网膜屏障通透性较DM组和正常对照组明显降低,差异均有统计学意义（P〈0.01）,且该变化呈时间依赖性。结论作为一种外源性PPAR-γ激动剂,罗格列酮能减少视网膜毛细血管的渗透性,对血-视网膜屏障具有保护作用,可能成为治疗糖尿病视网膜病变的新药物。

Effects of peroxisome proliferator-activated receptor-gamma excitomotor on blood-retinal barrier in rat with diabetic retinopathy

Background Diabetic retinopathy is a leading cause of acquired visual impairment in developed countries.It is a direct consequence of diabetic blood-retinal barrier breakdown.Much effort has been directed toward establishing effective treatments.However,there is no satisfactory pharmacological treatment for diabetic retinopathy.ObjectiveThe purpose of this study was to investigate the influence of peroxisome proliferator-activated receptor-gamma excitomotor（PPAR-γ）,rosiglitazone,on blood-retinal barrier in diabetic retinopathy induced by streptozotocin（STZ）.MethodsNinety clean Wistar rats were randomly divided into normal control group,diabetes mellitus（DM）group,DM＋rosiglitazone group.DM models were established in 60 rats by intraperitoneal injection of STZ.3mg/kg of rosiglitazone was intragastrically administered once per day in DM＋rosiglitazone group（30 rats）after modeling,and the same volume of DMSO was used in the same way in DM group and control group.All rats were sacrificed in 4,8 and 12 weeks,respectively.Retina digestion stretched preparation was performed,and the permeability of the blood-retina barrier was determined after infusion of Evans blue into ventriculus sinister.The peripheral cells and endothelial cells of retinal vessels were counted under the light microscope.ResultsThe blood glucose level was significantly elevated in various time points in DM＋ rosiglitazone group and DM group compared with control group（P0.01）.The blood capillary courser and the number and morphous of vessel wall cells were not abnormal in 4 weeks in DM group but the permeability value of the blood-retinal barrier was enhanced in comparison with control group（P0.01）.Retinal capillary wall pericytes were reduced,but the endothelial cells were increased,and capillaries were tortuous and broaden accompany with the high permeability value of the blood-retinal barrier in 8 and 12 weeks in DM group compared with control group（P0.01）.In every experimental session,the loss of the pericytes was much more,and the number of proliferative endothelial cells was decreased with the lower permeability value of the blood-retinal barrier in DM＋rosiglitazone compared with matched DM groups in a time-dependent manner（P0.01）.ConclusionAs a exogenous PPAR-γ excitomotor,rosiglitazone can protect the blood-retinal barrier in DM rats.It may become a new target for the treatment of diabetic retinopathy.