全反式维甲酸延缓糖尿病肾脏纤维化进展的实验研究

目的：探讨全反式维甲酸对延缓糖尿病大鼠肾脏纤维化的保护作用。方法：随机选择雄性SD大鼠分为空白对照组（NC）与造模组，制作糖尿病模型分为模型组（DM）与维甲酸治疗组（DM＋atRA）。于模型成型后分别于第8、12周观察各组大鼠24h尿蛋白（Ualb），内生肌酐清除率（Ccr），肾重／体重。肾脏病理及电镜观察肾小球基底膜厚度，免疫组织化学方法观察肾组织Ⅳ、Ⅲ型胶原表达。结果：维甲酸组肾重／体重、Ualb、Ccr较同时期模型组下降（P＜0．05），且12周大鼠肾组织细胞外基质（ECM）重要成分ColⅣ表达（5．75±0．41）、ColⅢ表达（4．98±1．37）与模型组比较显著减少（P＜0．01）。病理观察维甲酸组与模型组比较肾小球系膜细胞和内皮细胞增生减轻，足突融合改善，系膜基质增生缓解，基底膜厚度变薄，减轻了肾脏病理损害。结论：全反式维甲酸能减轻糖尿病大鼠早期肾脏病理损伤，减少细胞外胶原基质积聚，延缓肾脏纤维化。

The Inhibitive Effects of All-trans Retinoic Acid on Renal Fibrosis in Diabetic Rats

To explore the effect and mechanism of all-trans retinoic acid （atRA） on the fibrosis of kidney in STZ- induced diabetic rats. Methods：38 rats injected with streptozotocin（STZ） were randomly divided into model group （DM）and therapy group （DM ＋ atRA）. Other 12 normal rats were used as control group（NC）. The rats in DM ＋ atRA group were administrated atRA at a dosage of 20 mg·kg^-1 ·d^-1 ,and other rats were treated with normal saline. 24 h urinary protein（Ualb） ,blood urea nitrogen（BUN）, creatinine clearance（Ccr）, the ratio of renal weight/body weight （KW/BW）and renal pathological changes was evaluated. The expression of collagen were tested by immunohistochemisty technique 8 and 12 weeks after treated. Results： 24h Ualb, BUN,Ccr,the ratio of left renal weight/body weight were significantly lower in DM＋ atRA group than in DM group（P（0.05）. The expressions of collagen Ⅲ and Ⅳ of kidney in DM＋ atRA group were significantly lower than those in DM group （P〈0.01）. AtRA improved obviously the renal pathological changes in rats with diabetic nephropathy. Conclusion：AtRA can relieve renal injury and inhibit renal fibrosis in rats with diabetic nephropathy induced by STZ, which might be related to the down- regulation of the expression of collagen Ⅲ and Ⅳ in kidney.