[Effects of losartan on expressions of plasminogen activator and plasminogen activator inhibitor-1 of rat proximal tubular epithelial cells cultured with high glucose].

ABSTRACT

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.