PTEN、SHIP和CTMP对糖尿病肾病的作用及机制研究

肾小球硬化和肾小管间质纤维化是严重影响糖尿病肾脏功能的病理学改变。多种信号传导通路参与了肾小球系膜细胞和肾小管上皮细胞的细胞外基质分泌及硬化。近年来，PI3K/Akt通路被揭示与糖尿病肾系膜细胞及肾小管上皮细胞肥大和细胞外基质分泌相关，因此，针对PI3K/Akt通路进行调控干预，成为防治糖尿病肾小球和肾小管病变的研究方向。作为PI3K/Akt通路的负向调控因子，人第10号染色体缺失的磷酸酶及张力蛋白同源基因PTEN、SH2结构含磷酸肌醇SHIP和C末端调节蛋白CTMP是否在糖尿病肾小球硬化及肾小管间质纤维化中发挥作用及机制如何还未见系统报道。故本项目拟在糖尿病小鼠模型和体外培养的肾系膜细胞和肾小管上皮细胞，检测PTEN、SHIP和CTMP表达及对肾脏细胞外基质分泌和硬化的影响及机制，为糖尿病肾小球硬化和肾小管间质纤维化的延缓和防治提供新的研究思路，探索新的干预靶点。

The glomerulosclerosis and tubular interstitial fibrosis are the main features of diabetic nephropathy, leading to decreased renal function. Many studies revealed that multiple cell signal transduction pathway involved in extracellular matrix accumulation and sclerosis of renal mesangial cells and tubular cells. At present, it was confirmed that PI3K/Akt pathway mediated the hypertrophy and secretion of extracellular matrix in renal mesangial cells and renal tubular cells in diabetes. Therefore, the relative studies aimed at PI3K/Akt pathway became gradually the hot points to prevent the injury of renal glomerulus and tulule in diabetes. Now, it is not well known whether PTEN, SHIP and CTMP, known as negative regulators of PI3K/Akt pathway, involved in the glomerulosclerosis and tubular interstitial fibrosis in diabetic nephropathy. Therefore, we plan to, in the present study, detect the expression and effect of PTEN, SHIP and CTMP on extracellular matrix secretion and fibrosis of diabetic nephropathy through diabetic mice model, in vitro cultured renal mesangial cells and renal tubular cells. The results of the present research will supply the novel content and targets for the treatment of diabetic renal glomerulosclerosis and tubular interstitial fibrosis.