吡格列酮对糖尿病大鼠足细胞的保护作用

目的观察糖尿病（DM）大鼠肾小球上皮细胞蛋白-1（GLEPPl）表达及尿液足细胞（UPC）排泄的改变，吡格列酮对DM大鼠肾小球足细胞分布及UPC排泄的影响。方法大鼠分为3组，对照组；DM组；吡格列酮治疗组。腹腔注射链脲菌素诱导DM大鼠模型。实验10周末测24h尿蛋白定量（TP）、血清总胆固醇（TC）、血糖（BG）。间接免疫荧光法检测尿沉渣足细胞特异性标志蛋白podocalyxin以观察UPC排泄水平，检测GLEPPl以观察肾小球足细胞分布。结果DM组及吡格列酮治疗组UPC、TP、TC、BG较对照组明显升高（P〈O．01）。与DM组相比，吡格列酮治疗组TP、BG显著降低（P〈O．01），UPC及TC亦降低（P〈O．05）。病理组织肾小球荧光染色示GLEPPl在对照组正常，DM组明显缺失，吡格列酮治疗组呈节段性缺失。UPC与TP呈正相关（rs=0．41，P〈0，05），而与TC、BG无显著相关性（rs=0．19，0．23，P〉O．05）。结论肾小球足细胞缺失参与糖尿病肾病（DN）的发病，UPC检测可作为判断DN病情活动性的标志之一。吡格列酮可减轻DN大鼠尿蛋白，降低TC、血糖，减少足细胞脱落及尿液足细胞的排泄。

Pioglitazone Protects Podocytes in Diabetes Mellitus Rats

Objective To observe the expression of glomerular epithelial cell membrane protein-tyrosine phosphatase 1 （GLEPP1） and the excretion of urinary podocytes （UPC）, and the effect of pioglitazone on the distribution of podocytes in glomerulus and UPC excretion in diabetic mellitus （DM） rats. Methods Twenty-four healthy male Wistar rats were intraperitoneally injected with 65 mg/kg STZ to induce DM. Half of DM rats were intragastrically administered with 20 mg/（kg.d） pioglitazone once a day for 10 weeks. Another 10 normal Wistar rats without any special treatment served as controls. Ten weeks later, 24-hour total proteinuria （TP）, serum total cholesterol （TC） and blood glucose （BG） were measured. Podocyte-specific marker protein-podocalyxin （PCX） was detected in urinary sediment by immunofluorescene to observe the excretion of UPC. GLEPP1 was detected to observe the distribution of podocytes in glomerulus. Results UPC, TP, TC, BG in DM group and pioglitazone group were significantly higher than those in control group （P〈0. 01）. The levels of TP and BG （P〈0.01）, UPC and TC （P〈0. 05） were significantly lower in pioglitazone group than those in DM group. Histologically, the expression of GLEPP1 in glomeruli was normal in control group, obviously absent in DM group, and of focal absence in pioglitazone group. The levels of UPC showed a positive correlation with TP （rs=0. 41, P〈0. 05）, but was not correlated with TC and BO （rs= 0. 19, 0. 23, P〉0. 05）. Conclusion Podocyte loss in glomerulus leads to DM. Urinary podocytes can be one marker to predict the development of diabetic nephropathy. Pioglitazone contributes to decrease proteinuria, TC, BG and reduce the defluvium and excrection of podocytes.