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目的从足细胞分子nephrin和CD2相关蛋白(CD2AP)的变化探讨泼尼松、依那普利、氯沙坦3种药物抗蛋白尿作用的机制。方法予24只大鼠尾静脉一次性注射盐酸多柔比星,制备肾病模型,予6只大鼠尾静脉一次性注射等容积9 g/L盐水作为正常对照组。模型分为肾病组、泼尼松组、依那普利组及氯沙坦组各6只,分别灌服蒸馏水、泼尼松、依那普利、氯沙坦。采用实时荧光定量PCR、免疫组织化学检测大鼠肾小球nephrin、CD2AP的表达和分布变化。结果1.与正常对照组比较,肾病组24 h尿蛋白定量显著增加(P<0.01),且渐增加至6周;与肾病组比较,泼尼松组、依那普利组及氯沙坦组大鼠经治疗4周后尿蛋白定量均显著降低(Pa<0.01);3个治疗组间尿蛋白量无明显差异。2.nephrin mRNA、CD2AP mRNA表达变化:肾病组均显著高于正常对照组(Pa<0.01),泼尼松组、依那普利组、氯沙坦组均较肾病组降低(Pa<0.01),以泼尼松组下降最明显。3.nephrin、CD2AP蛋白水平变化:肾病组较正常对照组明显增加(Pa<0.05),泼尼松组、依那普利组、氯沙坦组均较肾病组降低(Pa<0.05),各治疗组间比较无明显差异。4.nephrin、CD2AP分布变化:肾病组肾小球nephrin、CD2AP染色增强,为连续性或不连续性颗粒样或节段性斑片状分布,泼尼松组、依那普利组、氯沙坦组中二者分布均较肾病组接近正常。结论泼尼松、依那普利、氯沙坦可通过稳定肾小球足细胞分子nephrin和CD2AP,从而起到减轻或消除蛋白尿的作用。
OBJECTIVE: To investigate the mechanism of antiproteinuria action of prednisone, enalapril and losartan on the changes of podocyte nephrin and CD2-related protein (CD2AP). Methods A total of 24 rats were injected intraperitoneally with doxorubicin hydrochloride into the caudal vein to prepare a nephropathy model. Six rats were injected intravenously with an equal volume of 9 g / L saline into the caudal vein as a control group. The model was divided into nephropathy group, prednisone group, enalapril group and losartan group, and each group was given distilled water, prednisone, enalapril and losartan respectively. The expression of nephrin and CD2AP in rat glomeruli was detected by real-time fluorescence quantitative PCR and immunohistochemistry. Compared with the normal control group, 24 h urinary protein in nephropathy group increased significantly (P <0.01), and increased gradually to 6 weeks. Compared with nephropathy group, prednisone group, enalapril group and losartan After 4 weeks of treatment, the proteinuria of urinary protein in rats was significantly decreased (Pa <0.01). There was no significant difference in urinary protein between the three treatment groups. The changes of nephrin mRNA and CD2AP mRNA expression in nephropathy group were significantly higher than those in normal control group (P <0.01). The prednisone group, enalapril group and losartan group were lower than those in nephropathy group (P <0.01) , The most obvious decline in the prednisone group. The changes of nephrin and CD2AP protein levels in nephropathy group were significantly higher than those in normal control group (P <0.05), and were lower in prednisone group, enalapril group and losartan group than in nephropathy group (P <0.05) There was no significant difference between the treatment groups. Nephrin, CD2AP distribution changes: nephropathy glomerular nephrin, CD2AP staining enhanced, continuous or discontinuous granular or segmental patchy distribution, prednisone group, enalapril group, chlorine The distribution of the two groups were close to normal in nephropathy group. Conclusions Prednisone, enalapril and losartan can reduce or eliminate proteinuria by stabilizing glomerular podocyte nephrin and CD2AP.