黄芪多糖对糖尿病大鼠早期多尿的保护作用

Protective action of astragalus polysaccharides on kidney in diabetic rats

目的观察黄芪多糖(astragalus polysaccharides,APS)对糖尿病(diabetes mellitus,DM)大鼠尿量、肾脏水通道蛋白2(aquaporin2,AQP-2)表达及肾脏超微结构的影响,以初步探讨其治疗糖尿病肾病(diabetic nephropathy,DN)的机制。方法采用链脲佐菌素(streptozotocin,STZ)制备DM大鼠模型,实验分4组:正常组、DM组、APS低剂量组和APS高剂量组,后两组应用APS200、400mg·kg-1·d-1腹腔注射6wk,用简易代谢笼法测各组大鼠24h尿量,电镜观察肾脏髓质超微结构,RT-PCR方法检测各组大鼠AQP-2 mRNA的表达。结果DM组大鼠尿量明显高于正常组(P<0.01),APS200、400mg·kg-1·d-1组大鼠尿量均明显高于DM组(P<0.01);电镜显示,DM组大鼠肾脏远端小管和集合管主细胞的超微结构与正常对照组比较呈现明显退行性改变,APS干预则可明显改善其超微结构的病变;RT-PCR检测,DM组大鼠肾脏髓质AQP-2 mRNA的表达明显高于正常组(P<0.01),APS低剂量组和高剂量组大鼠肾脏AQP-2 mRNA的表达较DM组明显下调(P<0.01)。结论APS治疗DN的作用机制可能与降低其肾脏髓质AQP2 mRNA的表达,增加尿量及改善肾髓质超微结构有关。

Aim To probe into the mechanism of the therapeutic effect of astragalus polysaccharides（APS）against diabetes mellitus rats by measuring renal medullary aquaporin-2（AQP-2）,the change of urinary volume in 24 hs,as well as observing kindey ultramicroscopic structures.Methods Thirty diabetes mellitus（DM）rats induced by streptozotocin（STZ）were randomly divided into three groups：DM group,APS 200 mg·kg-1·d-1 group,and APS high dosage group.Another 10 normal rats were taken as the control group.The drug was given by introperitonial injection for 6 weeks.A 24 h urine collection through simple metabolic cage was made to measure urinary volume;the RT-PCR technique was used to determine the levels of AQP-2 mRNA expression in kidney medulla.Kidney medulla ultramicroscopic structures were observed by TEM.Results Diabetic rats showed a significant increase in urinary volume compared with control rats.The urine amount of low and high dosage APS treatment could obviously increase the urinary volume（P0.05）;the expression of AQP-2 mRNA was up-regulated in the kidney of diabetic rats.Low and high dosage APS treatment could alleviate the over expression of AQP-2 mRNA（P0.05）.It showed degenerative changes of distal tubule and collecting tubes chief cells ultramicroscopic structures of the DM,APS low dose and high dose treatment group in contrast with the control group,while APS Long-term treatment could significantly improved the damage.Conclusion APS exerts its therapeutic effects on diabetes mellitus,which may be related to the significantly decreased expression of AQP-2 mRNA in the kidney medullary.