[Effect of GSK-3β inhibitor on the expression of RANK-RANKL in rats kidney tissue with diabetic nephropathy].

Objective: To investigate the effect and significance of GSK-3β inhibitor(LiCl)and RANK-RANKL on the renal tissue of diabetic nephropathy(DN) rats. Methods: SD rats were divided into normal control group (NC), DN model group (DN) and GSK-3β inhibitor intervention group (LiCl). Twenty-four hour urine protein of rats were determined by Coomassie brilliant blue. Kidney tissue sections were stained by HE. The expression of GSK-3β, RANK and RANKL protein were determined by immunohistochemistry staining. The mRNA of GSK-3β, RANK, RANKL was detected by RT-qPCR. Results: Compared with NC group[(14.72±3.37)g], the level of 24-hour urinary protein[(154.17±20.65)g] increased significantly in DN group; compared with DN Group, the level of 24-hour urinary protein [(107.22±31.15)g]decreased in LiCl group(P<0.05). Compared with NC group(2.10±0.60, 1.10±0.20, 1.21±0.20; 19.52±3.20, 1.80±1.10, 1.81±0.50), the pathological changes of renal tissues of DN group aggravated, the mRNA and expression of protein of GSK-3β, RANK and RANKL increased(9.10±2.15, 8.95±2.40, 9.90±2.60; 32.70±7.20, 19.20±4.32, 20.92±5.90); compared with DN group, the pathological changes of renal tissues of LiCl group alleviated, mRNA and the expression of protein of factors above declined(2.70±0.80, 2.32±0.65, 3.58±1.10; 22.35±3.25, 4.20±2.42, 5.90±2.36; P<0.05). Conclusion: RANK and RANKL play an important role in the development of DN, LiCl influence Wnt and NF-κB signal pathway down-regulating RANK and RANKL to suspend development of diabetic nephropathy.目的： 探讨GSK－3β抑制剂氯化锂及核因子κB受体活化因子(RANK)与核因子κB受体活化因子配体(RANKL)对糖尿病肾病(DN)大鼠肾组织病理改变的影响及意义。 方法： 将实验大鼠分成正常对照组(NC组)、DN模型组(DN组)和GSK－3β抑制剂氯化锂干预组(LiCl组)，各16只。考马斯亮蓝法检测24 h尿蛋白；肾脏组织切片行HE染色，观察大鼠肾脏病理改变；即时荧光定量逆转录聚合酶链反应(RT－qPCR)及免疫组织化学法(IHC)检测各组肾组织GSK－3β、RANK、RANKL的mRNA及蛋白的表达。 结果： 与NC组(14.72±3.37)g/24 h相比，DN组24 h尿蛋白水平(154.17±20.65)g/24 h升高；与DN组相比，LiCl组24 h尿蛋白水平(107.22±31.15)g/24 h下降(P<0.05)。与NC组[(2.10±0.60)、(1.10±0.20)、(1.21±0.20)；(19.52±3.20)、(1.80±1.10)、(1.81±0.50)]相比，DN组大鼠肾组织病理改变加重，GSK－3β、RANK、RANKL的mRNA及蛋白表达[(9.10±2.15)、(8.95±2.40)、(9.90±2.60)；(32.70±7.20)、(19.20±4.32)、(20.92±5.90)]升高；与DN组相比，LiCl组大鼠肾组织病理改变减轻，GSK－3β、RANK、RANKL的mRNA及蛋白表达[(2.70±0.80)、(2.32±0.65)、(3.58±1.10)；(22.35±3.25)、(4.20±2.42)、(5.90±2.36)；均P<0.05]下降。 结论： RANK和RANKL在DN发生发展中有重要作用；LiCl可通过激活Wnt信号通路，抑制GSK－3β，下调RANK和RANKL的表达，可一定程度上改善DN中的肾脏损害。.