Department of Internal Medicine of Renal Disease, Shanxi Dayi Hospital (Shanxi Academy of Medical Sciences), China.
Nephrology (Carlton). 2012 May;17(4):380-9. doi: 10.1111/j.1440-1797.2012.01563.x.
To further reveal the effects of leflunomide on renal protection and on inflammatory response using streptozotocin (STZ) induced diabetic rats.
Male Wistar rats were randomly divided into normal control group (NC), diabetic group (DM) and leflunomide treatment group (LEF). LEF group rats were given leflunomide (5 mg/kg) once daily. At the end of the 12th week, general biochemical parameters in three groups were determined. The renal histopathology was observed by light microscopy and electron microscopy. Further biochemical analysis of the gene and protein expression of nuclear factor kappa B (NF-κB), tumour necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and ED-1 positive cells in renal tissue were provided using real-time reverse transcription-polymerase chain reaction and immunohistochemistry.
Compared with NC group rats, systolic blood pressure, blood glucose (BG), glycohemoglobin (HbAlc), renal hypertrophy index, urine albumin excretion rate (AER) and serum creatinine were increased in DM group rats (P < 0.05). Treatment with leflunomide can improve these parameters except systolic blood pressure, BG and HbAlc. Creatinine clearance rate (Ccr) in the DM group was significantly lower than that of the NC group, and leflunomide can increase its level. Compared with DM group rats, the pathological damages were significantly relieved in LEF group rats. Compared with NC group rats, the gene and protein expressions of NF-κB, TNF-α, MCP-1 and ED-1 positive cells in renal tissue of DM group rats were highly upregulated (P < 0.01). Leflunomide suppressed their high expressions in renal tissue of diabetic rats.
Leflunomide can ameliorate the kidney structure and function injury of diabetic rats through suppressing the expression of NF-κB, TNF-α, MCP-1 and macrophage infiltration in renal tissue.
进一步揭示来氟米特对链脲佐菌素（STZ）诱导的糖尿病大鼠的肾脏保护作用和炎症反应的影响。
雄性 Wistar 大鼠随机分为正常对照组（NC）、糖尿病组（DM）和来氟米特治疗组（LEF）。LEF 组大鼠每日给予来氟米特（5mg/kg）。第 12 周末，测定三组大鼠一般生化指标。光镜和电镜观察肾脏组织病理学变化。实时逆转录-聚合酶链反应和免疫组织化学法检测肾组织核因子-κB（NF-κB）、肿瘤坏死因子-α（TNF-α）、单核细胞趋化蛋白-1（MCP-1）和 ED-1 阳性细胞的基因和蛋白表达。
与 NC 组大鼠相比，DM 组大鼠收缩压、血糖（BG）、糖化血红蛋白（HbAlc）、肾肥大指数、尿白蛋白排泄率（AER）和血清肌酐升高（P<0.05）。来氟米特治疗可改善上述指标，除收缩压、BG 和 HbAlc 外。DM 组大鼠肌酐清除率（Ccr）明显低于 NC 组，来氟米特可提高其水平。与 DM 组大鼠相比，LEF 组大鼠的病理损伤明显缓解。与 NC 组大鼠相比，DM 组大鼠肾组织 NF-κB、TNF-α、MCP-1 和 ED-1 阳性细胞的基因和蛋白表达明显上调（P<0.01）。来氟米特抑制糖尿病大鼠肾组织中这些高表达。
来氟米特通过抑制 NF-κB、TNF-α、MCP-1 和巨噬细胞浸润在肾组织中的表达，改善糖尿病大鼠的肾脏结构和功能损伤。
