摘要
目的研究高糖对正常大鼠肾近端小管上皮细胞纤溶酶原激活物(tPA和uPA)及其抑制物-1(PAI-1)表达的影响,并探讨血管紧张素受体阻滞剂氯沙坦对其改善作用。方法培养大鼠肾近端小管上皮细胞,并分组为正常对照组、甘露醇组(5 mmol/L D-葡萄糖+25 mmol/L甘露醇)、高糖组(30 mmol/L D-葡萄糖)、氯沙坦组(10-3mmol/L氯沙坦)、高糖+氯沙坦组(30 mmol/L D-葡萄糖+10-3mmol/L氯沙坦)。RT-PCR法检测各组细胞tPA、uPA及PAI-1 mRNA表达。结果与正常对照组比较,高糖组肾小管上皮细胞tPA和uPA mRNA表达下降(P<0.01),PAI-1 mRNA表达增加(P<0.01);氯沙坦可部分逆转高糖的作用,高糖加氯沙坦组tPA、uPA表达分别是高糖组的2.06倍、1.69倍(P<0.01),PAI-1表达为高糖组的44%(P<0.01)。结论高糖可使肾近端小管上皮细胞PA/PAI-1 mRNA异常表达,氯沙坦可以在肾小管中通过维持PA/PAI-1的平衡,对糖尿病肾病防治起一定的作用。
Objective To investigate the effects of high glucose on expressions of plasminogen activator(PA) and plasminogen activator inhibitor-1(PAI-1) of rat proximal tubular epithelial cells,and the role of angiotensin Ⅱ receptor antagonist Losartan.Methods The cultured NRK-52E cells(a renal proximal tubular epithelial cell line of rat origin) were divided into five groups: control group,mannitol group(5 mmol/L D-glucose plus 25 mmol/L mannitol),high glucose group(30 mmol/L D-glucose),losartan group(10^-3 mmol/L losartan),high glucose plus losartan group(30 mmol/L D-glucose plus 10^-3 mmol/L losartan).Semi-quantity RT-PCR was used to detect the expression of PA/PAI-1 mRNA.Results Compared with control group,the high glucose group decreased the expressions of tissue plasminogen activator(tPA) and urokinase plasminogen activator(uPA) mRNAs(P〈0.01) and increased PAI-1 mRNA expression(P〈0.01) in cultured NRK-52E cells.Losartan could reverse partly the expression of PA/PAI-1 mRNA.Compared to high glucose group,the PA mRNA expression was significantly increased(P〈0.01) and the PAI-1 mRNA expression was decreased greatly(P〈0.01) to high glucose plus losartan group.Conclusion The abnormal expression of PA/PAI-1 mRNA may play an important role in the accumulation of extracellular matrix(ECM) of diabetic nephropathy(DN).Losartan may keep the balance of PA/PAI-1 and have a protective effect on DN.
出处
《四川大学学报(医学版)》
CAS
CSCD
北大核心
2007年第5期813-815,共3页
Journal of Sichuan University(Medical Sciences)