内皮素与一氧化氮对肾病大鼠系膜细胞增生的影响

EFFECT OF ENDOTHELIN AND NITRIC OXIDE CONCENTRATIONS ON GLOMERULAR MESANGIAL CELL PROLIFERATION IN RATS WITH NEPHROTIC SYNDROME

目的 :研究阿霉素肾病大鼠不同时期血浆及肾局部内皮素 (Eendothelin ,ET)、一氧化氮 (Nitricoxide ,NO)的变化对系膜细胞增生的影响。方法 :4 8只SD大鼠随机分为对照组、肾病组及激素组。在实验第 1天 ,1周末 ,4周末 ,8周末应用生化法测定血浆及肾局部NO浓度及 2 4h尿蛋白排泌值 ,应用放射免疫法测定血浆及肾局部ET浓度 ,应用免疫组化法测定肾小球系膜细胞中CyclinD1,P2 7及PCNA阳性细胞率。结果 :第 1周末肾病组与激素组大鼠尿蛋白显著增高。第 4周末及实验末肾病组大鼠血浆及肾局部ET、尿蛋白、系膜细胞CyclinD1及PCNA阳性细胞率显著增高 ,P2 7阳性细胞率及血浆及肾局部NO显著降低 ,激素组大鼠血浆及肾局部ET、尿蛋白、系膜细胞CyclinD1及PCNA阳性细胞率较肾病组显著降低 ,P2 7阳性细胞率及血浆及肾局部NO显著增高。结论 :阿霉素肾病模型中 ,NO合成不足导致ET分泌增加 ,应是导致系膜细胞增生的重要原因。

Objective:To Investigate the effect of the variety of plasma and renal cortex nitric oxide (NO),endothelin(ET) concentrations on glomerular mesangial cell proliferation in rats with Doxorubicin-induced nephrotic syndrome. Methods:Forty-eight SD rats were randomly divided into control, nephrotic and dexamethasone-treated group.On the first day,at the end of the first week,the 4th week and the 8th week, we detected the excretion of 24h urinary protein, plasma and renal cortex nitric oxide (NO) concentrations by means of biochemistry assay, and plasma and renal cortex endothelin (ET) concentrations by means of Radioimmunoassay (RIA).The expressions of CyclinD1,P27 and PCNA in glomerular mesangial cells were measured by means of immunohistochemical technique.Results:At the end of the first week, the excretion of 24h urinary protein in nephrotic group and dexamethasone-treated group was significantly higher than that in control group (both P <0.01).At the end of the 4th week and the 8th week,plasma and renal cortex ET concentrations, the expression of CyclinD1 and PCNA in glomerular mesangial cells and the excretion of 24h urinary protein were significantly higher, and plasma and renal cortex NO concentrations, the expression of P27 in glomerular mesangial cells in nephrotic group were significantly lower than those in dexamethasone-treated group (all P <0.01). Conclusions:In the model of Doxorubicin-induced nephrotic syndrome rats,the glomerular mesangial cell proliferation is possibly due to the increased excretion of ET caused by decreased NO.