糖尿病大鼠肾小管间质早期病变及肾康注射液的干预治疗  

Early renal tubulointerstitial changes and their interventions with Shenkang Injection in diabetic rats

作　　者：刘洋[1] 马强[1] 杨光[1] 赵佳慧[1] 刘胜[1] 敖强国[1] 杜婧[1] 王晓华[1] 程庆砾[1] 

机构地区：[1]解放军总医院南楼临床部肾脏病科,北京100853

出　　处：《中华医学杂志》2015年第4期289-293,共5页National Medical Journal of China

基　　金：北京市自然科学基金（7122163）

摘　　要：目的 制作2型糖尿病大鼠模型,观察肾小管间质损伤是否为2型糖尿病的早期肾脏病理改变并探讨其干预方法及可能的机制.方法 采用高糖高脂饮食诱导联合小剂量链脲佐菌素（STZ）的方法建立2型糖尿病模型,同时设立正常对照组,采用肾康注射液（SKI）进行治疗,观察大鼠的一般状态、生化指标、尿微量白蛋白及尿N-乙酰-β-氨基葡萄糖苷酶（NAG）的改变;应用高胰岛素-正葡萄糖钳夹实验评估大鼠的胰岛素抵抗情况,肾组织高碘酸-雪夫染色（PAS染色）反应观察其病理变化;应用免疫组化方法检测肾组织Toll样受体4（TLR4）表达及肾间质CD68^＋细胞数.结果 糖尿病大鼠体质量减轻,尿微量白蛋白和尿NAG明显升高,胰岛素抵抗明显,肾小球体积增大,肾小管广泛空泡样变性,肾组织TLR4表达及肾间质CD68^＋细胞数明显增加[TLR4的累积吸光度（A）值：6 289.86±272.45与207.14-22.37,CD68^＋细胞数：8.79±0.79与1.23±0.52],SKI治疗后上述情况均有不同程度改善（均P ＜0.05）.结论 肾小管间质病变是2型糖尿病早期肾损害表现,SKI可以减轻肾脏的损伤,其机制可能与减少肾组织TLR4表达,抑制炎症介导的巨噬细胞浸润有关.Objective To explore whether renal tubulointerstitial lesions are early renal pathological changes and its interventions in diabetic rats.Methods The type 2 diabetic rat model was induced by a high-sugar and high-fat diet with a low-dose intraperitoneal injection of streptozotocin.And Shenkang Injection （SKI） was used as an intervention drug.A total of 30 Sprague-Dawley rats were divided randomly into diabetic （DM）,DM ＋ SKI （DMSK） and normal control （NC） groups.The general status,blood biochemical parameters,microalbuminuria and urinary N-acetyl-D-glueosaminidas （NAG） were recorded.The insulin resistance of diabetic rats was detected with hyperinsulinemic-euglycemic clamp test.Renal pathological changes were evaluated with periodic acid-Schiff （PAS） staining.The expression of Toll-like receptor 4 （TLR4） in kidney tissue and renal interstitial CD68^＋ cells was detected with immunohistochemistry.Results The levels of microalbuminuria,urinary NAG,glomerular volume,renal tubular score,TLR4 expression and renal interstitial CD68^＋ cells significantly increased in DM rats with body weight loss and insulin resistance （IOD value of TLR4：6 289.86 ± 272.45 vs 207.14 ± 22.37 ; CD68^＋ cells：8.79 ± 0.79 vs.1.23 ± 0.52）.All changes in DM rats improved after SKI intervention （P 〈 0.05）.Conclusion Renal tubulointerstitial lesions are early renal damages in type 2 diabetic rats.SKI can attenuate diabetic tubulointerstitial damage and delay the progression of diabetic nephropathy associated with the inhibition of TLR4 expression and inflammation-mediated macrophage infiltration.

关 键 词：糖尿病 2型 肾小管间质病变 TOLL样受体4 巨噬细胞 肾康注射液 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]