【摘要】 目的　探讨在实验性阿霉素肾病综合征 (NS)大鼠中 ,大量蛋白尿、低白蛋白血症在高胆固醇血症发生中的作用 ,以及肝脏对其的影响。方法　 2 3只大鼠随机分为经典阿霉素肾病组 (A组 )、新建大量蛋白尿模型组(B组 )及对照组 (C组 ) ,采用放射免疫法及狭线杂交 ,测定各组大鼠肝组织低密度脂蛋白受体 (LDLR)活力及其基因表达的改变。结果　B组大鼠出现同A组相似的大量蛋白尿及肾脏病理改变 ,肝组织LDLR活力在B组[(10 8.46± 2 1.38)ng/mg(以蛋白质量计 ) ]及A组 [(5 6 .89± 11.5 7)ng/mg(以蛋白质量计 ) ]均降低 ;但A组降低更明显 (P <0 .0 5 ) ,且与高胆固醇血症呈负相关 (r =- 0 .6 91,P <0 .0 1)。B组肝组织LDLR的基因表达较对照组升高 [(2 18± 5 0 ) % ](P <0 .0 5 ) ,A组则无变化 [(94± 18) % ](P >0 .0 5 ) ,与肝组织LDLR活力不一致 (r =- 0 .2 49,P >0 .0 5 )。结论　在实验性肾病综合征大鼠中 :①蛋白尿在高胆固醇血症的产生中是必需的 ,LDLR途径受损导致的LDL分解代谢下降 ,可能参与高胆固醇血症的发生。②白蛋白与脂蛋白代谢的紊乱似乎是平行的 ,有可能均为蛋白尿导致 ;但是这两者之间的相互影响不占主导地位。③其他与脂质代谢有关的器官、尤其是肝脏脂代谢功能的受损 ,可能在NS高胆固醇血症中更多还原

【Abstract】 Objective To further study the genesis of hypercholesterolemia in rats with nephrotic syndrome. Methods A new rat model of massive proteinuria was adopted, which was induced by bilateral renal-arterial perfusion with adriamycin. 24-hour urinary protein excretion, serum albumin concentration, serum cholesterole concentration, and hepatic low density lipoprotein receptor(LDLR)activity and its mRNA expression were determined in 3 groups of rats: group A, the classical model of adriamycin-induced nephropathy, B, the new model of massive proteinuria, and C, the normal control. Results Similar massive urine protein excretion and the same renal pathology were seen in group A and group B. The LDLR activity in liver was lowered in group A [(56.89±11.57)ng/mg Pr] and group B [(108.46±21.38)ng/mg Pr], with the former lowering more marked than the latter (P<0.05). The decreased level of liver LDLR activity was correlated to the hypercholesterolemia(r=-0.691,P<0.01). Compared with the normal, the LDLR mRNA expression in liver was increased twofold in group B [(218±50)%, P<0.05] , but not changed in group A [(94±18)%,P>0.05]. The altered mRNA expression level was not associated with the LDLR activity(r=-0.249,P>0.05). Conclusions ①In the rats with experimental nephropathy, while the massive proteinuria plays an essential role in generating hypercholesterolemia, the down regulation of LDL catabolism secondary to the compromise of LDLR route might be involved. ②The impairment of ablumin metabolism seemed to develop in parallel to that of lipoprotein, probably with both being resulted from massive proteinuria, but the interaction between the two is of minor importance. ③The impairment of lipid metabolism in concerned organs, especially that in the liver, may play a certain role in developing hypercholesterolemia in nephrotic syndrome.更多还原