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目的 观察霉酚酸酯在肾大部切除大鼠模型中对残肾的保护作用并探讨其可能的机制。方法 采用5/6肾大部切除模型,分别给予霉酚酸酯(MMF,15 mg·kg-1·d-1),福辛普利(25mg·kg-1·d-1)及两药合用。8周后观察大鼠24 h尿蛋白、BUN、Scr以及肾脏病理改变。并用免疫组化观察了胶原Ⅳ、纤连蛋白(FN)、增殖细胞核抗原(PCNA)和巨噬细胞趋化蛋白1(MCP-1)。用RT-PCR的方法测定了肾皮质中转化生长因子β1(TGF-β1)和组织性金属蛋白酶抑制剂1(TIMP-1)mRNA的表达。结果 两药均能减少尿蛋白,降低BUN和Scr,合用组减少最为明显。病理上,肾大部切除组可见基质增生,肾小球硬化,用药后病变减轻。其中应用MMF者可见PCNA和MCP-1明显减少。结论 在5/6肾大部切除模型中,MMF能通过抑制肾脏中的异常增殖、减少MCP-1的表达,下调TGF-β1和TIMP-1,减少细胞外基质,减少尿蛋白,从而明显减轻肾脏的损害。
Objective To observe the protective effect of mycophenolate mofetil on renal remnant in a rat model of subtotal nephrectomy and to explore its possible mechanism. Methods The 5/6 subtotal nephrectomy model was used and the patients were treated with mycophenolate mofetil (MMF, 15 mg · kg-1 · d-1), fosinopril (25 mg · kg-1 · d-1) Used together. After 8 weeks, 24 h urinary protein, BUN, Scr and renal pathological changes were observed. Collagen Ⅳ, fibronectin (FN), proliferating cell nuclear antigen (PCNA) and macrophage chemotactic protein 1 (MCP-1) were detected by immunohistochemistry. The expression of transforming growth factor-β1 (TGF-β1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA in renal cortex was determined by RT-PCR. Results Both drugs can reduce urinary protein, reduce BUN and Scr, combined with the most obvious reduction. Pathology, subtotal nephrectomy showed stromal hyperplasia, glomerular sclerosis, lesion after treatment. The application of MMF showed a significant reduction of PCNA and MCP-1. Conclusion In 5/6 subtotal nephrectomy model, MMF can significantly reduce the abnormal proliferation, decrease the expression of MCP-1, down-regulate the expression of TGF-β1 and TIMP-1, decrease the extracellular matrix and proteinuria in the kidney Kidney damage.