氯沙坦对高糖诱导大鼠肾近端小管上皮细胞纤溶酶原激活物及其抑制物表达的影响

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Ⅱ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(10-3 mmol/L氯沙坦)、高糖 氯沙坦组(30 mmol/L D-葡萄糖 10-3 mmol/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.

Effects of Losartan on Expressions of Plasminogen Activator and Plasminogen Activator Inhibitor-1 of Rat Proximal Tubular Epithelial Cells Cultured with High Glucose

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.