全反式维甲酸对糖尿病大鼠肾小管-间质纤维化的作用及机制  

Effect of all-trans retinoic acid on fibrosis of renal tubule-interstitium in rats with diabetes

作　　者：陈幼发[1] 熊羽 

机构地区：[1]武汉科技大学附属医院呼吸肾内科,430064 [2]湖北省武汉市第七医院,430064

出　　处：《重庆医学》2009年第15期1902-1904,1907,共4页Chongqing medicine

基　　金：重庆市科委自然科学基金资助项目(2004-67)

摘　　要：目的探讨全反式维甲酸对糖尿病大鼠肾小管-间质纤维化的作用以及对肾间质转化生长因子β1(TGF-β1)、α平滑肌肌动蛋白(α-SMA)表达的影响。方法24只链脲佐菌素(STZ)诱导的糖尿病大鼠模型,随机分为治疗组(T)、模型组(D)各12只、正常组12只(N),T组给予全反式维甲酸(atRA)(20 mg.kg-1.d-1)油溶液灌胃,D组和N组分别灌等量的植物油。4、8周每组各处死大鼠6只,测量24h尿微量清蛋白排泄率、肾重/体质量、血肌酐、血糖(BS)。肾组织PAS、Masson染色。免疫组化方法检测肾小管-间质TGF-β1、α-SMA的表达。结果atRA可减轻肾小球系膜区基质、细胞的增生,明显缓解肾小管-间质的纤维化。4周尿清蛋白的排泄率实验组低于模型组〔(3.08±0.48)μg/min与(3.35±0.56)μg/min,P<0.05〕,8周时尿清蛋白的排泄率明显低于同期模型组〔(2.49±0.40)μg/min与(4.53±0.87)μg/min,P<0.01〕;肾小管上皮细胞TGF-β1的表达明显低于模型组(P<0.01),肾小管-间质α-SMA的表达明显低于模型组(P<0.01)。结论atRA可减轻糖尿病大鼠肾小管-间质的纤维化,减少尿蛋白。可能通过下调肾小管-间质TGF-β1的表达、减少肾小管-间质肌成纤维细胞的数量,防止肾间质的纤维化,保护肾功能。Objective To explore the effect of all trans retinoic acid on fibrosis of renal tubule-interstitium and expression of TGF-β and α-SMA of renal tubule-interstitium in rats with diabetes. Methods Twenty-four rats injected with streptozotocin（STZ） were randomly divided into model （D）and therapy group （T）,in addition, 12 normal rats as control group （N）. The rats in therapy group were administrated by atRA,which was dissolved by vegetable oil,at a dosage of 20mg · kg ^-1· d ^-1 ,D and N group were treated with vegetable oil. The excretory rate of urinary protein, ratio of kidney and body weight, serum creatinine, BS were measured after 4 and 8 weeks, the morphological changes were observed by PAS and Masson＇s staining. The expression of TGF-β1 andα- SMA in renal tubule-interstitium was assessed by immunohistochemical method. Results atRA reduced proliferation of mesangial cell and matrix,significantly attenuated fibrosis of renal tubule-interstitium. The excretory rate of urinary protein in T group was significantly lower compared with I） group [（ 3.08 ± 0.48）μg/min vs （3.35 ± 0.56）μg/min, P〈 0.05; （2.49 ±0.40）/,g/min vs （4.53±0.87）μg/min, P〈0.01） respectively after 4,8 weeks. The expression of TGF-β1 and α SMA in renal tubule-interstitium was significantly down-regulated compared with model（P〈0.01）. Conclusion atRA alleviates the fibrosis of renal tubule-interstitium in rats with diabets, reduces urinary protein and prevents fibrosis of renal interstitium by down-regulation of TGF-β1 expression and reduction of myofibroblast in renal tubule-interstitium.

关 键 词：全反式维甲酸 转化生长因子Β1 Α平滑肌肌动蛋白 肾间质纤维化 

分 类 号：R96[医药卫生—药理学]