HMG-CoA还原酶抑制剂对肾病综合征大鼠肝脏低密度脂蛋白受体表达的影响

Effects of HMG-CoA Reductase Inhibitor on the Expression of Low Density Lipoprotein Receptor in Liver of Nephrotic Rats

目的观察在大鼠肾病综合征模型中使用3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂洛伐他汀(Lovastatin)治疗对肝脏低密度脂蛋白(LDL)受体表达的影响,探讨他汀类药治疗肾病综合征高脂血症的机制。方法大鼠2次尾静脉注射阿霉素建立肾病综合征大鼠模型;采用灌胃法给予大鼠洛伐他汀治疗2周。采用Western blot和RT-PCR技术分别检测LDL受体蛋白和其mRNA在肝脏的表达,同时检测大鼠相关血生化指标。结果肾病综合征大鼠洛伐他汀治疗2周后,血清总胆固醇、LDL胆固醇和三酰甘油以及尿蛋白均显著降低(均P<0.05),血清白蛋白显著升高(P<0.05),血肌酐在各组间差异无显著性意义(P>0.05);肝脏LDL受体蛋白较肾病综合征组显著增加(P<0.01);肝脏LDL受体mRNA水平在各组间差异无显著性意义。结论肾病综合征大鼠经洛伐他汀治疗后,其肝脏LDL受体缺乏得到明显改善,伴随的高脂血症也得到明显改善。

Objective To observe the effects of HMG-CoA reductase inhibitor on the expression of LDL receptor in liver of nephrotic rats and the mechanism of Lovastatin treating hyperlipidemia in nephrotic syndrome. Methods Adriamycin-induced nephrotic rat models were established by a twice injection of adriamycin via the tail vein. Nephrotic rats were treated with either Lovastation or placebo for 2 weeks. The expression of LDL receptor mRNA and protein in liver tissues and serum biochemistry parameters were examined. Results After 2 weeks of Lovastatin administration, serum levels of total cholesterol, LDL cholesterol, triglyceride and urinary protein excretion were significantly decreased, and serum albumin was significantly increased. No significant difference was found in serum creatinine among the 3 groups. LDL receptor protein deficiency in liver was significantly ameliorated in study group. There was no significant difference in the expression of LDL receptor mRNA in liver among the 3 groups. Conclusion HMG-CoA reductase inhibitor Lovastation improved LDL receptor deficiency in liver and ameliorated the associated hyperlipidemia in the nephrotic rats.