[氯沙坦对高糖培养的大鼠近端肾小管上皮细胞纤溶酶原激活物及纤溶酶原激活物抑制剂-1表达的影响]

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

作者信息

Pu Li-jun, Huang Song-min, Liu Fei

机构信息

Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2007 Sep;38(5):813-5.

PMID:17953365

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.

摘要

目的

探讨高糖对大鼠近端肾小管上皮细胞纤溶酶原激活物（PA）及纤溶酶原激活物抑制剂-1（PAI-1）表达的影响，以及血管紧张素Ⅱ受体拮抗剂氯沙坦的作用。

方法

将培养的NRK-52E细胞（大鼠源性肾近端肾小管上皮细胞系）分为五组：对照组、甘露醇组（5 mmol/L D-葡萄糖加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）、高糖加氯沙坦组（30 mmol/L D-葡萄糖加10⁻³ mmol/L氯沙坦）。采用半定量RT-PCR检测PA/PAI-1 mRNA的表达。

结果

与对照组相比，高糖组培养的NRK-52E细胞中组织型纤溶酶原激活物（tPA）和尿激酶型纤溶酶原激活物（uPA）mRNA表达降低（P < 0.01），PAI-1 mRNA表达增加（P < 0.01）。氯沙坦可部分逆转PA/PAI-1 mRNA的表达。与高糖组相比，高糖加氯沙坦组PA mRNA表达显著增加（P < 0.01），PAI-1 mRNA表达显著降低（P < 0.01）。