肾病幼鼠肾组织尿激酶型纤溶酶原激活物及其抑制物mRNA与蛋白表达的特点和ACEI干预的影响

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目的 探讨肾病幼年大鼠肾组织尿激酶型纤溶酶原激活物 (uPA)及其特异性抑制物(PAI 1)mRNA与蛋白质表达的特点 ,及予血管紧张素转换酶抑制剂 (ACEI)苯那普利治疗的影响。方法 采用阿霉素诱导的肾病大鼠为动物模型 ,予ACEI治疗 12周后测大鼠体重、血压、尿蛋白及血生化各项指标的变化 ,同时用Northern杂交及免疫组化染色等方法 ,检测肾组织uPA和PAI 1的mRNA及蛋白表达情况 ,并比较各组间的变化特点。结果 肾病大鼠肾组织PAI 1mRNA吸光度值为 1 6 ,蛋白质组化半定量为 (6 5 3± 10 2 ) % ,uPAmRNA吸光度值为 0 4 ,蛋白组化半定量为 (30 3± 4 2 ) % ;正常对照组PAI 1mRNA吸光度值为 0 5 ,蛋白质组化半定量为 (10 6± 2 4 ) % ,uPAmRNA吸光度值为0 7,蛋白组化半定量为 (85 3± 3 0 ) % ,两组两指标比较差异均有显著意义。经治疗后肾组织PAI 1mRNA吸光度值 0 9,蛋白组化半定量为 (2 0 7± 6 5 ) % ,趋于下降 ,uPAmRNA吸光度值为 0 8,蛋白组化半定量为 (93 1± 5 1) % ,趋于增高 (P <0 0 1)。结论 肾病病变进展中可出现纤溶系统的平衡紊乱 ,ACEI治疗可改善PA/PAI 1的异常表达 ,防止细胞外基质的异常沉积 ,阻止肾小球硬化和间质纤维化病变的进展 Objective To investigate the expression of mRNA and protein of urokinase-type plasminogen activator (uPA) and its specific inhibitor (PAI 1) in kidney of juvenile rats with nephropathy and to explore the effect of angiotensin converting enzyme inhibitor (ACEI) Effects of NAP treatment. Methods Adriamycin-induced nephrotic rats were used as animal models. The changes of body weight, blood pressure, urinary protein and blood biochemical parameters of rats after ACEI treatment for 12 weeks were measured. Northern blotting and immunohistochemical staining were used to detect the changes of blood glucose, The mRNA and protein expression of uPA and PAI 1 in renal tissue were detected, and the changes between the groups were compared. Results The nephropathy rat renal tissue PAI 1 mRNA absorbance value of 16, the protein semiquantitative (6 5 3 ± 10 2)%, uPA mRNA absorbance value of 0 4, protein semiquantitative (30 3 ± 4 2) %; PAI 1mRNA absorbance of normal control group was 0 5, semi-quantitative proteome was (106 ± 2 4)%, uPA mRNA absorbance was 0 7, semi-quantitative proteomics was (85 3 ± 3 0)%, Two groups of two indicators have significant differences. After treatment, the PAI 1 mRNA absorbance value of renal tissue was 0.9, and the semiquantitative expression of PAI was (207 ± 65)%, which tended to decrease. The absorbance of uPA mRNA was 0 8, and the protein semiquantitative was (93 1 ± 5) 1)%, tends to increase (P <0 0 1). Conclusion The progression of nephropathy may appear the imbalance of fibrinolytic system. ACEI treatment can improve the abnormal expression of PA / PAI 1, prevent the abnormal deposition of extracellular matrix and prevent the progression of glomerulosclerosis and interstitial fibrosis.
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