洛伐他汀对糖尿病大鼠肾脏组织的保护作用及其调控

Protective effects of Lovastatin on early diabetic renal tissue and the possible mechanism

目的探讨洛伐他汀对糖尿病大鼠肾功能的保护作用及核转录因子cAMP反应元件结合蛋白1(CREB1)的作用。方法雄性Wistar大鼠行右肾切除术2周后,随机分为3组右肾切除对照组、糖尿病组和洛伐他汀治疗组。4周后各组选取6只大鼠,收集血尿测定生化指标;免疫组化检测肾皮质磷酸化CREB1(PCREB1)及增殖细胞核抗原(PCNA)的表达特征,Western印迹及RTPCR检测肾皮质CREB1磷酸化(活性)及mRNA的变化。结果4周时糖尿病组血脂、尿素氮、肌酐清除率和尿蛋白排泄率增加,同时PCNA、PCREB1蛋白及mRNA表达明显增强;而洛伐他汀组虽然血脂无明显改善,但肾功能损伤明显减轻,同时PCNA、PCREB1蛋白及mRNA表达有不同程度的降低。结论洛伐他汀对糖尿病大鼠肾功能具有保护作用,机理是通过调节PCREB1蛋白及mRNA的表达从而减轻糖尿病早期细胞增殖肥大来实现。

Objective To investigate the protective effects of Lovastatin on renal function in experimental diabetic nephropathy in rats.and the function of cAMP-responsive element binding protein (CREB_1) in this duration. Methods Diabetes was induced in male Wistar rats by intrapetitoneal injection of STZ(65mg/kg). Three groups were divided as: Sham group, diabetic control group and Lovastatin treatment group. Lovastatin(20mg/kg) was administered daily by gavage from the next day of the induction diabetes for 4 weeks. Upro,ucr in urine and Glu, Scr, BUN in serum were determined. Immunohistochemistry and computer image-pattern analysis system were used to analyze expression of PCNA and p-CREB_1.Western blot were performed to valuate the expression of p-CREB_1 with their specific corresponding antibodies.CREB_1 mRNA was measured by RT-PCR. Results After Lovastatin treatment, renal function were ameliorative in diabetic rats. Decrements were also found in the expression of and PCNA,p-CREB_1 and its mRNA in the treatment group compared with the diabetic group.Conclusion Inhibition of glomerular cAMP-responsive element binding protein1 may be responsible for the Lovastatin protective function that allevate the renal proliferation and hypertrophy in diabetic rats.