全反式维甲酸对糖尿病大鼠肾小管—间质中肌成纤维细胞的作用

Effect of all-trans retinoic acid on myofibroblast of renal tubule-interstitium in diabetic rats

目的观察全反式维甲酸对糖尿病大鼠肾小管—间质中肌成纤维细胞的影响。方法链脲佐菌素(STZ)诱导的糖尿病模型大鼠24只随机分为实验组(T)、模型组(D)各12只,正常组(N)健康大鼠12只,T组给予全反式维甲酸(20mg·kg-1.d-1)植物油溶液灌胃,D组和N组分别灌注相同等量的植物油。4、8周时每组各处死大鼠6只,测量24h尿微量白蛋白排泄率、肾重/体重、血肌酐、血糖(BS)。肾组织PAS、Masson’s染色,免疫组化检测肾小管—间质α-平滑肌肌动蛋白(α-SMA,肌成纤维细胞的标记)的表达。结果肾组织PAS、Masson’s染色可见T组肾小球系膜细胞和基质的增生明显低于D组,肾小管上皮细胞的肿胀、空泡变性以及肾间质的增生明显好于D组;4周时尿微量白蛋白的排泄率T组低于D组[(3.1±0.5)μg/minvs(3.4±0.6)μg/min,P<0.05],8周时更加明显[(2.5±0.4)μg/minvs(4.5±0.9)μg/min,P<0.01];4、8周血肌酐T组分别低于同期D组[(56±6)μmol/Lvs(65±4)μmol/L,P<0.05;(48±3)μmol/Lvs(69±6)μmol/L,P<0.01],肾重/体重T组分别低于同期D组(6.0±0.4vs6.7±0.6,P<0.05;5.1±0.6vs7.8±1.0),血糖差异无统计学意义[(30.1±3.2)mmol/Lvs(28.3±3.5)mmol/L,P>0.05;(28.8±5.3)mmol/Lvs(31.0±3.3)mmol/L,P>0.05];肾小管—间质α-SMA表达T组明显低于D组。结论全反式维甲酸可减轻糖尿病大鼠肾小管—间质的损害,减少蛋白尿、肾小管—间质肌成纤维细胞的数量,防止肾间质的纤维化。

Objective To observe the effect of all-trans retinoic acid （atRA） on myofibroblast of renal tubule-interstitium. Methods The diabetic models of 24 rats were set up by injecting streptozotocin （STZ）. The rats were randomly divided into model group （group D） and theatment group （group T）, in addition, 12 normal rats were used as control group （group N）. The rats in group T were administrated atRA, which was dissolved by vegetable oil, at a dose of 20 mg· kg^ -1· d^ -1 , the rats in group D and group N were given with same dose of vegetable oil. The excretory rate of urinary protein , the ratio of kidney and body weight, creatinine, blood sugar（BS） were measured after 4 and 8 weeks, the morphological changes were observed by PAS and Masson＇ s staining, the α-SMA expression in renal tubule-interstitittm was assessed by immunohistochemical method. Results The atRA reduced prolife ration of mesangial cell and matrix, and significantly relieved the damage of renal tubule and reduced matrix of renal interstitium. The excretory rate of urinary protein in group T was significantly lower than that of group D respectively after 4, 8 weeks [（3.1±0.5）μg/min vs （3.4±0.6）μg/min, P 〈0.05;（2.5±0.4）μg/min vs （4.5 ± 0.9）μg/min, P 〈0.01]. Blood creatinine, the ratio of kidney and body weight in group T were significantly lower than those of group D respectively after 4,8 weeks [ （56 ± 6） μmol/L vs （65 ± 4） μmol/L, P 〈 0.05 ; （48 ± 3 ） μmol/L vs （ 69 ± 6 ）μmol/L, P 〈 0.01 ; （6.0 ± 0.4） vs （6.7 ± 0.6）, P 〈 0.05; （5.1 ± 0.6） vs （7.8 ± 1.0） 1, but there was no significant difference in BS [ （30.1 ± 3.3）mmol/L vs （28.3 ±3.5）mmol/L, P 〉 0.05; （28.8 ± 5.3）mmol/L vs （31.0 ±3.3） mmol/L, P 〉 0.05]. α-SMA expression in renal tubule-interstitium in group T was significantly down-regulated, as Compared with that of group D. Conclusion The atRA could alleviate the damage of renal tubule of diabetic nephropathy rats, and could reduce urinary protein, prevent fibrosis of renal interstmum by inhibiting the proliferation of myofibroblast in renal tubule-interstitium.