氟伐他汀对糖尿病大鼠肾组织核因子-κB活性的影响

目的：观察氟伐他汀对实验性2型糖尿病大鼠肾组织中核因子-κB（NF-κB）活化的影响。方法：应用单侧肾切除后饮食加小剂量链脲佐菌素（STZ）方法，制备2型糖尿病肾病（DN）大鼠模型。将实验动物随机分为假手术组、2型糖尿病组及氟伐他汀治疗组（2mg·kg^-1·d^-1）。给药治疗6周后，检测各组动物血糖、血脂、血肌酐（Scr）、24h尿蛋白定量（TP／24h）等指标。采用电泳迁移率变动分析（EMSA）方法检测NF-κB活性变化，采用RT—PCR方法检测单核细胞趋化蛋白-1（MCP-1）mRNAg达水平。结果：小剂量氟伐他汀未影响血糖、血脂。治疗6周后，可明显降低2型DN大鼠肾组织中NF-κB活性，减少MCP-1 mRNA表达，并降低蛋白尿。结论：氟伐他汀对实验性2型糖尿病大鼠具有非依赖降脂的肾脏保护作用，其机制至少部分与降低肾组织中NF-κB活性，下调MCP-1基因表达有关。

Effects of Fluvastatin on Activation of Renal Nuclear Factor-kappa B in Experimental Type 2 Diabetic Rat

Objective：To investigate the effects of fluvastatin on activation of renal NF-κB in type 2 diabetic rat. Methods： A rat modal of type 2 diabetic nephropathy （DIN） was established successfully by combination of dietary- induced insulin resistance and low-dose STZ- induced hyperglycemia after unilateral nephrectomy. Female SD rats were＇randomly divided into three groups： control rats, type 2 diabetic rats and type 2 diabetic rats treated with fluvastatin （2 mg·kg^-1·d^-1）. After 6 weeks, blood glucose, serum triglyceride, cholesterol,serum creatinine,and urinary protein were measured respectively. EMSA was used to detect NF-κB activation. RT - PCR technique was used to detect MOP - 1 gene expression. Results： Fluvastatin at lower doses, which did not influence blood glucose and lipid level, significantly inhibited expression of NF -κB activation, down - regulated expression of MCP - 1 mRNA and lowered urine protein excretion after 6 weeks. Conclusion： Fluvastatin can prevent renal damage in progressive diabetic kidney disease, which is independent from cholesterol - lowering effect. The mechanism may be associated partially with clown - regulating renal NF -κB activation and MCP - 1 mRNA expression in type 2 DN.