PPARγ激动剂对肾病大鼠血清和肾组织Angpt14以及尿蛋白排泄的影响

摘要

Objective To investigate the effect of PPAR gamma agonist on the excretion of proteinuria and the Angptl4 level in serum and renal tissue of purinamycin-induced nephrotic rats. Methods Sixty male SD rats, purinamycin-induced nephrotic rat models of minimal change disease were established by intraperitoneal injection of puromycin aminonucleoside (PAN)(150 mg/kg), the health control group received equal volume of normal saline by intraperitoneal injection. Then rats were randomly divided into saline control group (intragastric treatment with normal saline), PAN control group (intragastric treatment with normal saline after injection of PAN ), Pio0 group (intragastric treatment with pioglitazone was the same day as PAN injection ), Pio4 group (intragastric treatment with pioglitazone 4 days after PAN injection) and Pio10 group (intragastric treatment with pioglitazone 10 days after PAN injection ). the dose of pioglitazone was given with 10 mg/ (kg · d).24 h urine volume, blood and renal tissue specimen were collected in 4 d, 10 d and 21 d after model building. Biochemical method was used to measure total protein of 24 h urine, serum total protein, serum creatinine, total cholesterol and triglyceride. Elisa method was used to detect the serum Angptl4 level of rats. RT-PCR and Western blot technology were used to detect mRNA and protein expression of kidney tissue in rats. Results Tenth days after PAN injection, levels of proteinuria in Pio0 and Pio4 group decreased significantly compared with PAN group [Pio0 group (16.08 + 3.50) vs (70.80±8.12) mg/24 h; Pio4 group (33.81 + 4.16) vs(70.80 + 8.12) mg/24 h; P＜0.05]. The expression of Angptl4 mRNA in renal tissue in Pio0 and Pio4 group showed a significant reductioncompared with PAN group (P＜0.05), conversely the expression of serum Angptl4 increased significantly compared with PAN group [Pio0 group (104.11±10.56) vs (71.90± 14.91) ng/mL, Pio4 group (104.88±6.29) vs (71.90± 14.91) ng/mL; P＜0.05]. Conclusion PPAR gamma agonist may reduce proteinuria by increasing the serum expression of Angptl4 and reducing the expression of Angptl4 in renal tissue.%目的 观察PPARγ激动剂对嘌呤霉素肾病大鼠血清和肾组织Angpt14以及尿蛋白排泄的作用并探讨其机制.方法 雄性SD大鼠60只.腹腔注射嘌呤霉素氨基核苷(PAN, 150 mg/kg)制作微小病变大鼠肾病模型,对照组腹腔注射等体积生理盐水,随机分成生理盐水对照组(生理盐水灌胃治疗)、PAN组(PAN注射后行生理盐水灌胃治疗)、Pio0组(PAN注射当天开始吡格列酮灌胃治疗)、Pio4组(PAN注射第4天后开始吡格列酮灌胃治疗)、Pio10组(PAN注射第10天后开始吡格列酮灌胃治疗),吡格列酮灌胃治疗剂量为10 mg/ (kg · d).各组大鼠分别在造模后4、10、21 d收获大鼠并留取24h尿液、血标本及肾组织标本,测定24h尿蛋白、血清总蛋白、血肌酐、总胆固醇、三酰甘油,ELISA法测定大鼠外周血Angptl4水平,RT-PCR及Western blot法测定肾组织Angptl4 mRNA和蛋白表达水平.结果 在嘌呤霉素注射后第10天,Pio0、Pio4组与PAN组相比,大鼠尿蛋白量明显降低(P＜0.05);肾组织中Angpt14 mRNA和蛋白表达量较PAN组明显下降(P＜0.05),外周血Angptl4表达量较PAN组增多(P＜0.05).结论 PPARγ激动剂可能通过增加肾病大鼠血清Angptl4的表达和减少肾脏组织Angptl4表达来降低蛋白尿,起到保护肾脏的作用.