噻唑烷二酮类药物对实验性糖尿病大鼠早期视网膜病变的影响

目的 观察噻唑烷二酮类（TZDs）药物罗格列酮和吡格列酮对实验性糖尿病大鼠早期视网膜病变的影响。 方法 在40只大鼠中利用链脲佐菌素（STZ）一次性腹腔注射制作糖尿病大鼠模型36只，另4只为正常对照组。将生存至病程6个月以上的24只大鼠分组，分别行玻璃体腔注射罗格列酮和吡格列酮（每组各10只），另4只不注射药物作为糖尿病阳性对照。眼球石蜡切片进行血管内皮生长因子（VEGF）免疫组织化学链霉卵白素生物素复合物（SABC）法、VEGF mRNA原位杂交、末端脱氧核糖核酸转移酶介导的dUTP缺口末端标记（TUNEL）法检测细胞凋亡，并比较注射TZDs大鼠和对照组大鼠视网膜VEGF表达及细胞凋亡的不同。 结果 正常大鼠视网膜VEGF免疫组织化学染色及原位杂交检测结果均为阴性。注射罗格列酮和吡格列酮大鼠与糖尿病阳性对照大鼠相比，视网膜VEGF表达阳性细胞率有所下降，但VEGF mRNA的阳性表达以及视网膜细胞凋亡检测结果无明显差别。 结论 TZDs药物罗格列酮和吡格列酮对STZ诱导的糖尿病大鼠视网膜VEGF的总体表达具有一定的抑制作用，但并不影响该细胞因子在视网膜上的生成。 (中华眼底病杂志, 2006, 22: 7-10)

Effect of thiazolidinediones on early retinopathy in rats with experimental diabetes

Objective To determine the effect of thiazolidinediones (TZDs) on early retinopathy in rats with experimental diabetes. Methods In 40 rats, diabetic models were set up in 36 by one-off intraperitoneal injection with streptozotocin (STZ), and other 4 were in the normal control group. Twenty-four diabetic rats with the disease-duration of more than 6 months underwent intravitreous injection (with rosiglitazone or pioglitazone in 10 rats, respectively), and the rest 4 rats weren′t injected with drugs as the diabetic positive control group. Immunohistochemical treptomycin-avidin-biotin-complex (SABC) method, in situ hybridization of retinal vascular endothelial growth factor (VEGF) mRNA, and TdT-dUTP terminal nick-end labelling (TUNEL) were performed on the ocular paraffin section to detect the cellular apoptosis. The difference of VEGF expression and cellular apoptosis between TZDs and control group was observed and analyzed. Results The results of immunohistochemical staining and hybridization in situ were negative in the normal control group. The positive expression rate of VEGF was lower in rosiglitazone and pioglitazone group than which in the diabetic positive control group, and there was no obvious differences of positive expression of VEGF mRNA and cellular apoptosis between the 2 groups. Conclusion TZDs (rosiglitazone and pioglitazone) may inhibit the positive expression of VEGF protein in retina of STZ-induced diabetic rats to some extent, but not affect the growth of VEGF in retina. (Chin J Ocul Fundus Dis, 2006, 22: 7-10)