厄贝沙坦对高胆固醇血症大鼠肾PAI-1活性的影响

Effect of Irbesartan on PAI-1 Activity in Renal Cortex in Hypercholesterolemia Rats

目的 :①了解纤溶酶原激活物抑制剂 1(PAI 1)在高胆固醇大鼠血及肾皮质的表达及其与肾脏损害的关系 ;②探讨厄贝沙坦对高胆固醇血症PAI 1活性的影响。方法 :Wistar大鼠随机分为 3组 :正常组、高脂组和厄贝沙坦组 ,12周后测定血浆及肾皮质PAI 1活性。石蜡切片行HE、PAS染色观察一般病理变化 ,免疫组化检测纤连蛋白和Ⅳ型胶原的表达。结果 :与对照组相比 ,高脂组血浆及肾皮质PAI 1活性明显升高 ,系膜基质增多 ,系膜区纤连蛋白和Ⅳ型胶原增多 ,厄贝沙坦组肾皮质PAI 1活性和纤连蛋白、Ⅳ型胶原较高脂组低 ,但仍较正常组高 ,PAI 1活性与纤连蛋白和Ⅳ型胶原呈显著正相关。结论 :高胆固醇血症大鼠肾皮质PAI 1活性增加 ,可能与肾小球细胞外基质积聚有一定关系 ,可能参与脂质肾损害的进展 ,厄贝沙坦可部分阻止这种作用。

Objective: To investigate the protein expression of plasminogen activator inhibitor(PAI 1) in renal tissue of hypercholesterolemia rats and the effect of Irbesartan. Methods: Forty Wistar rats were divided into three groups in random, one group were fed on hyperlipid diet (H group),one group were fed on hyperlipid diet and Irbersartan (HT group),the other group were fed on normal diet(C group). The renal pathological changes were observed, the activity of PAI 1 in serum and renal cortex were determined after 12 weeks and the protein expression of collagen Ⅳ and fibronectin were examined by immunochemistry. Results: Compared with control group,PAI 1 activity in serum and renal cortex and the expression of collagen Ⅳ and fibronectin increased significantly in H group. PAI 1 activity have a positive relationship with collagen Ⅳ and fibronectin. Conclusion: Increased PAI 1 activity in serum and renal cortex may be related to glomerular matrix accumulation and may stimulate the progress of lipoid nephrosis. Irbersatan can partly prevent this effect.