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目的观察霉酚酸酯(MMF)对糖尿病大鼠肾组织单核细胞趋化蛋白-1表达和炎症细胞浸润的影响,并探讨其对肾脏的保护作用及机制。方法SD大鼠随机分为三组:对照组(C组)、糖尿病组(D组)和糖尿病治疗组(M组,20mg.kg-1.d-1)。大鼠单侧肾脏切除后,腹腔注射链脲菌素(STZ)成糖尿病模型,对照组仅注射等量缓冲液。观察12周后,检测大鼠血糖(BG)、血尿素氮(BUN)、血肌酐(Scr)、肾脏肥大指数(肾重KW/体重BW)、肌酐清除率(Ccr)和24小时尿蛋白(24Upro)。肾组织做常规光镜和电镜检查,观察组织的形态结构。用免疫组织化学方法检测肾组织中巨噬细胞抗原(CD68)和增殖细胞核抗原(PCNA)的蛋白表达。用半定量RT-PCR的方法检测肾组织中单核细胞趋化蛋白-1(MCP-1)的mRNA的表达。结果与对照组相比,糖尿病组大鼠BG、KW/BW、24Upro、BUN、Scr、Ccr均显著上升(P<0.05或0.01);肾小球系膜区相对面积和肾小球基底膜厚度均显著增加(P<0.01);肾组织内CD68和PCNA的蛋白质表达和MCP-1的mRNA表达均显著上调(P<0.05或0.01)。在糖尿病治疗组,上述指标除血糖外都被显著抑制(P<0.05或0.01)。结论在糖尿病大鼠模型中,MMF能减少尿蛋白,对糖尿病肾病有保护作用,其机制可能与其抑制炎症因子-MCP-1的表达,下调CD68和PCNA的水平,减少肾组织单核/巨噬细胞的聚集有关。
Objective To observe the effect of mycophenolate mofetil (MMF) on the expression of monocyte chemoattractant protein-1 and infiltration of inflammatory cells in diabetic rats, and to explore its protective effect on the kidney and its mechanism. Methods SD rats were randomly divided into three groups: control group (C group), diabetes group (D group) and diabetes treatment group (M group, 20mg.kg-1.d-1). Rats after unilateral nephrectomy, intraperitoneal injection of streptozotocin (STZ) into the diabetic model, the control group was injected with an equal amount of buffer. After 12 weeks of observation, the blood glucose (BG), blood urea nitrogen (BUN), serum creatinine (Scr), renal hypertrophy index (renal weight KW / BW), creatinine clearance (Ccr) and 24- 24Upro). Renal tissue routine light microscopy and electron microscopy to observe the morphological structure of the organization. Immunohistochemistry was used to detect the protein expression of macrophage antigens (CD68) and proliferating cell nuclear antigen (PCNA) in renal tissues. The mRNA expression of monocyte chemoattractant protein-1 (MCP-1) in renal tissue was detected by semi-quantitative RT-PCR. Results Compared with the control group, the levels of BG, KW / BW, 24Upro, BUN, Scr and Ccr were significantly increased in diabetic rats (P <0.05 or 0.01). The relative area of glomerular mesangial area and glomerular basement membrane thickness (P <0.01 or 0.01). The protein expression of CD68 and PCNA and the mRNA expression of MCP-1 in renal tissues were significantly increased (P <0.05 or 0.01). In the diabetes treatment group, the above indexes were significantly inhibited except blood sugar (P <0.05 or 0.01). Conclusions In diabetic rat model, MMF can reduce urinary protein and protect diabetic nephropathy. The mechanism may be related to its inhibitory effect on the expression of MCP-1, downregulation of CD68 and PCNA, and decrease of monocyte / macrophage Related to the accumulation of cells.