全反式维甲酸对糖尿病大鼠肾小管-间质TGF—β1和α-SMA表达的影响

Effect of all-trans retinoic acid on the expression of TGF-β1 and α-SMA of renal tubule-interstitium in rats with diabetic nephropathy

目的探讨全反式维甲酸对糖尿病大鼠肾小管-间质转化生长因子α（TGF—β1）、d平滑肌肌动蛋白（α—SMA）表达的影响。方法24只链脲佐菌素（STZ）诱导的糖尿病大鼠随机分为治疗组（T），模型组（D）各12只，12只正常组（N），T组给予全反式维甲酸20mg／（kg·d）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，测量尿微量白蛋白排泄率、肾重／体重、血肌酐（Scr）、血糖。肾组织PAS、Masson染色。免疫组化方法检测肾小管-间质TGF—β1、α—SMA表达。结果全反式维甲酸可减轻肾小球系膜区基质、细胞的增生，明显缓解肾小管的损伤，肾间质的基质减少。4周尿微量白蛋白的排泄率实验组低于模型组[（3．08±0．48）μg／minVS（3．35±0．56）μg／min，P〈0．05]，8周时尿微量白蛋白的排泄率明显低于同期模型组[（2．49±0．40）μg／minVS（4．53±0．87）μg／min，P〈0．01]；肾小管-间质TGF-β1、α—SMA表达明显低于模型组（P〈0．01）。结论全反式维甲酸可减轻糖尿病大鼠肾小管-间质的损害，减少尿蛋白。可能通过下调肾小管-间质TGF—β1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 the expression of TGF-β1 and α-SMA of renal tubule-interstitium in rats with diabetic nephropathy. Method 24 rats injected with streptozotocin （STZ） were random divided into model （D） and therapy group （T） , in addition, 12 normal rats were used as control group （N）. The rats in therapy group were administrated with atRA, which was dissolved by vegetable oil, at a dosage of 20mg/（ kg . d）. D and N group were treated with vegetable oil. Excretory rate of urinary protein, the ratio of kidney and body weight, serum creatinine, BS were measured after 4 and 8 weeks. The morphological changes were observed by HE, PAS and Masson＇s staining. The expression of TGF-β1 and αSMA in renal tubuleinterstitium were assessed by immunohistochemical method. Results atRA reduced proliferation of mesangial cell and matrix, significantly attenuated damage of renal tubule and reduced extracellular matrix of renal interstitium. Excretory rate of urinary protein in T group was significantly lower after 4 and 8 weeks, compared with D group [ （ 3.08 ± 0. 48 ） μg/min VS （ 3.35 ± 0. 56 ） μg/min, P 〈 0. 05 ; （ 2. 49 ± 0. 40 ）μg/min VS （ 4. 53 ± 0. 87 ）μg/min, P 〈 0. 01 ]. The expression of TGF-β1 and αSMA in renal tubule-interstitium were significantly down-regulated, compared with model group（ P 〈 0. 01 ）. Conclusion atRA alleviated the damage of renal tubule of diabetic nephropathy, reduced urinary protein, prevented fibrosis of renal interstitium by down-regulation of TGF-β1 expression and reduction of myofibroblast in renal tubule-interstitium.