复方甘草酸苷片对局灶节段性肾小球硬化大鼠肾功能及CYP11B2、11b-HSD2基因表达的影响

Effect of Compound Glycyrrhizin Tablets on Renal Function and Expression of CYP11B2 and 11β-HSD2 Genes in Focal Segmental Glomerulosclerosis Rats

关键词:  复方甘草酸苷片  局灶节段性肾小球硬化  醛固酮合成酶  11β-羟化甾体脱氢酶

Key words:  Compound Glycyrrhizin tablets  focal segmental glomerulosclerosis  CYP11B2  11β-HSD2

摘要:

目的 探讨复方甘草酸苷片对局灶节段性肾小球硬化（focal segmental glomerulosclerosis，FSGS）大鼠肾功能的保护作用及对醛固酮合成酶（CYP11B2）和11β-羟化甾体脱氢酶（11b-HSD2）基因表达的影响。方法 采用单侧肾切除合并尾静脉注射阿霉素构建FSGS模型，实验分成正常组、模型组、复方甘草酸苷片组、联合干预（复方甘草酸苷片+依普利酮）组和依普利酮组5组，各干预组按相应剂量每天1次灌胃给药，连续10周。测定尿蛋白、血清肌酐、尿素氮、白蛋白、胆固醇、甘油三酯、低密度脂蛋白胆固醇水平，HE染色及透射电镜观察肾组织病理损伤的改变。RT-PCR检测肾组织CYP11B2和11b-HSD2的基因表达水平。结果 和模型组比较，复方甘草酸苷片组FSGS大鼠24 h尿蛋白、血清胆固醇水平显著下调（P<0.05或P<0.01），血清白蛋白水平显著增高（P<0.01）；依普利酮组FSGS大鼠血清肌酐、尿素氮、甘油三酯、胆固醇及24 h尿蛋白均显著下降（P<0.05或P<0.01），血清白蛋白水平显著增高（P<0.01）。HE染色结果显示，复方甘草酸苷片组基底膜增厚及系膜基质增生程度较模型组有所减少。透射电镜结果显示，复方甘草酸苷片组的足突融合程度较模型组有所减轻。RT-PCR结果表明复方甘草酸苷片干预后能够显著下调CYP11B2的表达。未见复方甘草酸苷片和依普利酮联合用药的协同效果。结论 复方甘草酸苷片可明显改善FSGS大鼠肾功能损伤，减轻肾组织病理损伤，延缓FSGS的进程。本实验中，复方甘草酸苷片和依普利酮联合用药未见明显的协同作用。

Abstract:

OBJECTIVE To explore the effect of Compound Glycyrrhizin tablets on renal function and the expression of aldosterone synthase(CYP11B2) and 11β-steroid dehydrogenase(11β-HSD2)genes in rats with focal segmental glomerulosclerosis (FSGS). METHODS Rat model with FSGS was established by unilateral nephrectomy combined with adriamycin injection into the tail vein. The experiment were randomly divided into five groups that was control group, model group, Compound Glycyrrhizin tablets group, combined intervention(Compound Glycyrrhizin tablets+eplerenone) group and eplerenone group, each intervention group was intragastrically administered at the corresponding dose, once a day for 10 weeks. Urine protein, serum creatinine, urea nitrogen, albumin, cholesterol, triglyceride, low density lipoprotein cholesterol levels was determined, HE staining and transmission electron microscopy were used to observe the changes of renal tissue pathological damage. RT-PCR detected the expression of CYP11B2 and 11β-HSD2 in kidney tissues. RESULTS Compared with the model group, the 24 h urine protein and serum cholesterol of FSGS rats in Compound Glycyrrhizin tablets group decreased significantly(P<0.05 or P<0.01), and serum albumin increased significantly(P<0.01). The serum creatinine, urea nitrogen, triglyceride, cholesterol, and 24 h urine protein of FSGS rats in eplerenone group were significantly decreased compared with the model group(P<0.05 or P<0.01), and serum albumin was significantly higher than the model group(P<0.01). HE staining showed basement membrane thickening and mesangial matrix hyperplasia were reduced in Compound Glycyrrhizin tablets group. The result of transmission electron microscopy showed that the degree of foot process fusion in the Compound Glycyrrhizin tablets group was alleviated compared with the model group. RT-PCR results showed that Compound Glycyrrhizin tablets intervention could down-regulate CYP11B2 expression. There was no significant synergistic effect in the combined intervention group. CONCLUSION Compound Glycyrrhizin tablets can significantly improve renal function damage in FSGS rats, reduce renal tissue pathological damage, and delay the progression of FSGS. In this experiment, the synergistic effect is not observed in the combined intervention of the Compound Glycyrrhizin tablets and the eplerenone.