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

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。

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

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.