摘要目的 通过检测各组大鼠肾组织中糖原合酶激酶-3β(GSK-3β)与核因子(NF)-κB的表达,研究GSK-3β抑制剂对糖尿病肾病大鼠Wnt和NF-κB信号通路的影响及意义.方法 将大鼠分成正常对照(NC)组、糖尿病肾病模型(DM)组和GSK-3p抑制剂干预(DI)组.检测各组大鼠血糖、24 h尿蛋白,HE染色法观察肾组织病理改变,应用免疫组织化学法检测GSK-3β、NF-κB在肾组织中的表达,采用real-time荧光定量聚合酶链反应(RT-qPCR)法检测上述因子mRNA在肾组织中的表达.结果 DM成模10周后,DM组及DI组血糖值分别为(23.2±5.4) mmol/L与(25.0±4.0)mmoVL,并且两组的尿蛋白值分别为(185.2 ±35.6) g/24 h与(179.6 ±44.7)g/24 h,均显著高于NC组[(12.0 ±2.5)g/24 h与(18.6 ±3.1)g/24 h,均P＜0.01].后经LiCl治疗2周,DI组大鼠血糖值为(17.6±2.1)mmol/L,尿蛋白值为(106.9±30.0) g/24 h,均明显低于DM组[(24.6±2.4) g/24 h与(185.0 ±46.0) g/24 h,均P＜0.05].与NC组相比,DM组大鼠肾组织出现病理改变,且GSK-3p与NF-κB的活性增强,mRNA及蛋白表达显著升高(P＜0.05);与DM组相比,DI组大鼠肾组织病理改变减轻,上述因子的活性减弱,mRNA及蛋白表达明显下降(P＜0.05).结论 GSK-3p与NF-κB在糖尿病肾病中的活性表达正相关,Wnt与NF-κB信号通路在糖尿病肾病的发生发展中有重要作用.

abstractsObjective To explore the impact of glycogen synthase kinase-3β (GSK-3[β) on Wnt and NF-κB pathways in a rat model of diabetic nephropathy (DN).Methods SD rats were randomly divided into normal control group (NC), DN model group (DM) and GSK-3β inhibitor group (DI).Blood glucose and 24-hour urine protein were monitored in three groups.Renal tissue samples were stained by HE.The expression of GSK-3β and NF-κB proteins was studied by immunohistochemistry.GSK-3β and NF-κB mRNAs were detected by RT-qPCR.Results Ten weeks after STZ injection, the level of blood glucose increased significantly in DM group [(23.2 ± 5.4) mmol/L] and DI group [(25.0 ± 4.0) mmol/L],compared with NC group, and the level of 24-hour urinary protein increased significantly in DM group [(185.2 ± 35.6) g/24 h] and DI group [(179.6 ± 44.7) g/24 h], compared with NC group.Two weeks after LiCl injection, the level of blood glucose and 24-hour urinary protein decreased in DI group (17.6 ±2.1) mmol/L, (106.9 ±30.0)g/24 h], compared with DM Group.Compared with NC group, pathological changes of the kidney of DM group aggravated along with increased mRNA and protein expression of GSK-3[β and NF-κB.But the pathological changes of the kidney in DI group alleviated along with declined mRNA and protein expression of GSK-3[β and NF-κB as compared with DM group(all P ＜ 0.05).Conclusions NF-κB protein expression positively correlates with the GSK3 β expression.Wnt and NF-κB signal pathways play an important role in the development of diabetic nephropathy.