Influence of astragalus polysaccharide on kidney status and fibrosis indices of a rat model of streptozotocin-induced diabetic nephropathy

摘要

目的:探讨黄芪多糖(APS)对糖尿病肾病模型大鼠的肾脏指数及纤维化情况的影响.方法:健康雄性SD大鼠72只,随机分为空白对照组(NC,n=24)、模型组(DNM,n=24)和黄芪多糖治疗组(DNM+APS,n=24).DNM和DNM+APS组大鼠进行单侧肾切除术,并接受链霉素注射液(STZ,65 mg/kg)建立DN模型,NC组不做任何处理.DNM+APS组于术后第1周起皮下注射APS 50 IU/kg/d,NC和DMS组与皮下注射等量生理盐水.术后3、8、13周分批随机处死各组大鼠,每组各6只,腹主动脉取血检测Scr、BUN;处死前1天将大鼠置于代谢笼中(禁食,不禁水)收集24h尿液,测定24h尿蛋白定量.术后第14周,每组随机测量6只大鼠体重、肾脏指标,目内眦取血测定血糖;用HE染色观察肾间质病理改变;免疫组化检测TGF-β1,α-SMA蛋白表达.结果:DNM组大鼠肾脏组织病理结果显示肾小球系膜基质增生、肾小管萎缩、基底膜增厚.相比之下,经APS(50 IU/kg/d)治疗的STZ诱导的糖尿病肾病大鼠肾脏病理改变明显减轻,提示APS对STZ诱导的DN大鼠肾组织有修复作用.实验结果表明,APS可以减轻肾损伤,有效提高糖尿病肾病大鼠的体重,肾功能损害早期可得到改善.在疾病的后期,24小时尿蛋白显著减少.此外,APS可以抑制肾脏中TGF-β1和α-SMA的表达.结论:APS可以显著改善DNM大鼠早期肾功能受损情况并修复肾间质受损状态,其有效机制可能与通过抑制肾脏中TGF-β1和α-SMA的表达来延缓DNM大鼠肾间质纤维化进展有关.%Object: To examine the effect of astragalus polysaccharide (APS) on kidney status and fibrosis indices of rats with diabetic nephropathy. Methods:72 male rats were randomly divided into three groups:negative control group (NC, n=24);diabetic nephropathy model group (DNM, n=24);and diabetic nephropathy model with APS group (DNM+APS, n = 24). Rats of the DNM and DNM +APS groups were subjected to both unilateral nephrectomy and administered streptozotocin (STZ) injection (65 mg/kg). DNM+APS group rats were administered 50 IU/kg/d APS by subcutaneous injection from the first week after operation until death. The NC and DNM group rats were subcutaneously injected with an identical volume of physiological saline. At weeks 3, 8, and 13 after the operation, 6 rats from each group were randomly sacrificed and blood was collected to measure serum creatinine and blood urea nitrogen. On the day before sacrifice, the rats were placed in a metabolic cage for 24 h to collect urine. At week 14 after the operation, 6 rats from each group were randomly selected to measure body weight and kidney index. Blood was collected to measure blood glucose. The kidneys were harvested to detect pathological changes by hematoxylin and eosin staining. Results:Histological assessment of DNM rats suggested damage symptoms as evidenced by hyperplasia of the glomerular mesangial matrix, atrophia of the kidney tubules, and thickening of the basement membrane. In contrast, STZ-induced diabetic nephropathy rats treated with APS (50 IU/kg/d) showed significantly improved histological results, suggesting that APS has beneficial effect on renal tissues in STZ-induced DNM rats. Our results also indicated that APS relieved renal injury and effectively improved body weight in DNM rats. The ratio of kidney weight to body weight was reduced and the early stage of renal function damage was improved after APS treatment. In the later stages of the disease, the 24 h urinary protein significantly decreased. Moreover, APS down-regulated TGF-β1 andα-SMA expression of the kidney. Conclusion: APS significantly improved renal tubular interstitial injury in DNM rats and the early stage of renal function damage. The mechanism may be related to downregulation of the expression of TGF-β1 and α-SMA which delays the progression of renal interstitial fibrosis in DNM rats.