缬沙坦抑制大鼠糖尿病视网膜病变中VEGF表达的实验研究

目的探讨缬沙坦抑制大鼠糖尿病视网膜病变中VEGF表达的作用。方法80只龄雄性Wistar大鼠,经单次腹腔链脲佐菌素(STZ)后诱导糖尿病模型,随后随机分为模型对照组(8只)和缬沙坦大剂量(24只)、中剂量(24只)及小剂量(24只)干预组,干预组分为第4周开始给药(8只),第8周开始给药(8只)和第12周开始给药(8只)三组。每日分别给于缬沙坦40mg、10mg及4mg/kg体重灌胃治疗,而对照组则采用等量的生理盐水灌胃。于干预后4周时各组摘除眼球,视网膜石蜡包埋切片,免疫组化染色,用计算机-图像分析仪对视网膜中血管内皮细胞生长因子进行平均灰度和面密度分析。结果缬沙坦治疗组大鼠同对照组比较,前者视网膜中VEGF显著降低,尤其以40mg/kg.d组更为明显,而且治疗组中第4周时上述生长因子较第8周和第12周显著降低。结论早期应用大剂量AT1R拮抗剂可以降低VEGF的表达,从一定程度上改善DR,对视网膜起到保护作用。

论著缬沙坦抑制大鼠糖尿病视网膜病变中VEGF表达的实验研究

Objective To evaluate the effect of valsartan on VEGF involving into diabetic retinopathy.Methods Eighty male Wistar rats were obtained.Rat models of diabetes mellitus were established by intraperitoneal injection of 50 mg.kg-1 streptozotocin,subsequently those models were randomly divided into diabetic retinopathy(DR,n=8) group and treatment groups with valsartan 40,10 and 4 mg.kg-1.d-1 by intragastric administration.At the same time control group accepted same amount of physiological saline.The treatment were began after 4,8,12 weeks.4 weeks late,eyeballs of mice from each group were enucleated,embedded in paraffin to make tissue sections for immunohistochemistry analysis.The instrument for computer image-analysis was used to analyze the expression of vascular endothelial growth factor(VEGF) in ganglion cell layer of retina.Results After treatment with 4 and 10 mg.kg-1 valsartan,the expression of VEGF was reduced than diabetic controls and further reduced with 40 mg.kg-1 of valsartan.Moreover,the treatment for 4 weeks could more evidently suppress the expressions of VEGF in retina of diabetic rats than treatment for 8 and 12 weeks.Conclusion Treatment of angiotensin 1 type receptor(AT-1R) antagonists could exert a potentially therapeutic effect upon the retina of DR.