高脂饮食对阿霉素肾病大鼠肾小球系膜基质的影响

目的 探讨高脂饮食对阿霉素肾病大鼠肾小球硬化的影响。方法 应用病理、免疫组化及分子生物学方法结合图像分析技术,观察高脂饮食对大鼠血胆固醇、尿蛋白、肾脏病理形态学改变以及肾小球系膜基质产生的影响。结果 在非肾病组及肾病组,高脂饮食大鼠的血胆固醇较标准饮食大鼠明显升高,分别为（ 2.2± 0.3） g/L vs(0.9± 0.1)g/L(P

Effect of high-lipid diet on glomerular mesangial matrix in adriamycin-induced nephrotic rats

OBJECTIVE: To determined the effect of hypercholesterolemia induced by high-lipid diet on glomerulosclerosis. METHODS: Urinary protein excretion and serum cholesterol were assayed, Image analysis and techniques of pathology, immunohistochemistry, molecular biology were used to determine morphological changes in glomeruli and the production of glomerular mesangial matrixes in adriamycin-induced nephrotic syndrome (NS) and non-NS rats fed with standard chow and high-lipid chow. RESULTS: The serum total cholesterol level was significantly higher in rats with high-lipid chow in both non-NS[(2.2 +/- 0.3) g/L vs (0.9 +/- 0.1) g/L, P < 0.01] and NS[(9.5 +/- 0.2) g/L vs (2.3 +/- 0.3) g/L, P < 0.01]. The urinary protein excretion was significantly higher in the high-lipid diet rats than that in standard chow rats [(76.2 +/- 24.2) mg/24 h vs (44.8 +/- 13.6) mg/24 h, P < 0.05] in NS rats. Significant increases in the mesangial matrix and mesangial cells were observed in rats with high-lipid diet in both NS and non-NS group. Especially, more obvious pathological changes were found in NS group, such as lipid deposits and foam cell formation in mesangial areas, and progressing to focal and segmental glomerulosclerosis in some glomeruli. The immunohistochemical assay showed that the production of fibronectin was increased in the rats with high-lipid diet in non-NS group, whereas, the production of three major components (collagen IV, fibronectin, and laminin) was increased in NS group, especially in the rats with high-lipid chow. The increased expression of laminin mRNA was also detected with slot blotting in both NS and non-NS rats with high-lipid chow, and it was more obvious in the rats with NS. CONCLUSION: Our findings indicated that diet-induced hyperlipidemia can lead to over-production of mesangial matrix components, and further aggravate glomerulosclerosis in adriamycin-induced nephrosis.